 Patients who have survived critical illness are at increased risk for long term morbidity and mortality. Maybe we tend to forget this fact, as we lose sight of these patients when they leave our unit. But this is especially true for ICU patients aged 65 and older! There have been clues that influenza vaccination might reduce morbidity after surviving critical illness and Christiansen et al. have looked exactly into this topic. The investigators examined whether an influenza vaccination (flu shot) affects the 1-year risk of myocardial infarction, stroke, heart failure, pneumonia, and death among ICU survivors aged 65 and older. The investigators Performed a nationwide population-based cohort study They used the Danish Intensive Care Database To evaluate a total 89'818 ICU survivors from 2005 until 2015 It is noteworthy that Influenza vaccinated patients (these were 39% of all) were older, had more chronic diseases and used more prescription medications! Their findings show that 1. Influenza vaccinated patients showed an 8% decreased risk of death and a 16% reduced risk of hospitalisation for stroke within one year 2. Cardiac surgery patients were the subgroup that profited most 3. Unfortunately, no significant association was found for the risk of hospitalisation for myocardial infarction, heart failure or pneumonia.  The flu shot saves lives! This is another strong hint, that the influenza vaccination is clearly of benefit to all adults aged 65 and older. This is especially true for ICU survivors! Christiansen at al. Intensive Care Med 2019 Jul;45(7):957-967. Also worth mentioning: Not only influenza A but also Influenza B infection can pose a risk for severe secondary infection in previously healthy and younger persons. Aebi et al. BMC Infect Dis 2010 Oct 27;10:308.  When the FDA approved dexmedetomidine (DEX) in 1999, intensive care medicine had a novel and highly promising drug at its disposal. Compared to clonidine, dexmedetomidine is an 8 times more selective, central alpha 2 agonist, which binds to all 3 subtypes of the receptor. The properties of this substance were auspicious, among them: sedation, analgesia, neuroprotective effects and a lack of respiratory depression. - Sedation decreases sympathetic activity, aggression and leads to a non-REM-like state, which of all sedatives comes closest to natural sleep. Cognitive functions are maintained, and patients usually remain arousable. - Dexmedetomidine has a particular analgesic effect via modulation in the region of the posterior horn of the spinal cord. This has shown to reduce the use of opiates. - By reducing cerebral catecholamines, dexmedetomidine exerts a neuroprotective effect. - Interestingly, sedation with dexmedetomidine is not associated with significant respiratory depression. These properties pointed to a wide range of applications in the intensive care unit: - Sedation in patients with non-invasive ventilation - Weaning of invasively ventilated patients - Agitated delirium - Treatment of various withdrawal syndromes - Fiberoptic awake intubation in theatre conditions Dexmedetomidine comes with its side effects, though. Most commonly bradycardia and hypotension are observed, making second and third-degree heart block a contraindication. Also, nausea and a dry mouth might be seen. Interestingly, prolonged use might be associated with some extent of discontinuation syndrome similar to clonidine. This involves hypertension, tachycardia, nervousness etc. What Evidence Do We Have So Far? |
The SPICE III Trial |  |
Precisely this question was now addressed by Shehabi et al., published in the NEJM
They performed an
International (8 countries, 74 ICU's), randomised controlled, unblinded trial
In which they evaluated
4000 ICU patients that were expected to need mechanical ventilation for at least 48 hours and required sedation for safety or comfort
They compared
Patients sedated with propofol, midazolam or other agents as prescribed by the treating physician with patients receiving dexmedetomidine as a continuous infusion
(if DEX alone was insufficient, other agents could be added! In fact, 64% of patients also received propofol, 3% midazolam and 7% received both)
They found
1. No difference in 90-day mortality (primary outcome) and
2. No difference in death after 180 days, institutional dependency at 180 days, mean cognitive decline and assessment of the quality of life. Also no difference in median days free from coma to day 28 and median ventilator-free days at day 28 (all secondary outcomes)
3. Dexmedetomidine was though associated with significantly more events of bradycardia, hypotension (no further info on the use of vasopressors) and asystoles (14 vs 2; 7 required mechanical resuscitation measures)
- DEX is an attractive sedative in certain situations (alcohol withdrawal, other forms of delirium, weaning process etc.), BUT
- DEX doesn't seem to provide any advantage in the sedation of mechanically ventilated patients in the ICU and
- Might be problematic due to adverse cardiovascular effects, especially in this group of patients
Shehabe et al. N Engl J Med 2019; 380:2506-2517
Did you Know?
Apparently, intranasal dexmedetomidine seems used successfully for sedation in adults and children. J Clin Neurophysiol. 2019 May 16.
Acute decompensated heart failure comes in many ways as remains a challenge for optimal treatment since various conditions can cause it, e.g. advanced chronic heart failure, cardiogenic- and septic-shock, cardiac- and non-cardiac surgery, etc. Among many other interventions, the infusion of positive inotropes is often used on one side and vasodilators on the other side to stabilize the situation and improve cardiac function. Despite all these measures, the re-admission rate and mortality remain a significant problem among these patients.
While Levosimendan is still under investigation in the U.S., it is used worldwide for the short-term treatment of acutely decompensated severe chronic heart failure, especially when other treatment options have failed. Some recommend the usage of this drug in a different setting like sepsis-related heart failure or coronary heart disease.
How does Levosimendan work?
Levosimendan has some remarkable properties, which are mainly caused by three mechanisms:
1. Enhancement of the calcium sensitivity of the myofilament by binding to troponin C.
2. Opening of adenosine triphosphate-sensitive potassium (KATP) channels in vasculature smooth muscle.
3. Opening of mitochondrial KATP channels.
These mechanisms result in a positive inotropy of the heart, an increase in stroke volume (SV) and therefore, cardiac output (CO). Besides, it's vasodilatory properties seems beneficial for coronary perfusion and reduce pulmonary capillary wedge pressure (PCWP).
All these effects do not appear to induce an unfavourable energy balance in the myocardial cell, and also the oxygen demand is not increased.
ScienceDirect.com
So what's the Evidence?
The Small Bits and Pieces
First publications back in the 90ies and early 2000s were indicative for the properties of levosimendan. Three studies were randomized and double-blinded but very low in patient numbers and therefore not powered enough to provide substantial evidence. Their statements were also not concerning patient outcome or mortality, but its results confirmed that levosimendan enhances cardiac output without oxygen wasting, is well tolerated and leads to favorable hemodynamic effects.
Lilleberg et al. Eur Heart J. 1998;19:660–668.
Ukkonen et al. Clin Pharmacol Ther. 2000;68:522–531.
Nieminen et al. J Am Coll Cardiol. 2000;36:1903–1912.
In 2003 Kivikko et al. published further data from another small trial indication that its beneficial effects (decreases in left and right heart filling pressures and in SVR, as well as increases in stroke volume and cardiac index) are maintained for at least 24 hours after discontinuation of a 24-hour infusion. At this point, it is worth mentioning that the author published these findings as a current employee of Orion Pharma, which manufactures levosimendan.
Kivikko et al. Circulation. 2003;107:81–86.
Further data indicated that its effect might be sustained for up to at least a week, although also this study included only 22 patients!
8. Lilleberg et al. Eur J Heart Fail. 2007;9:75–82.
A Lancet publication in 2002 by Follath et al. presented a multicentre, randomized, double-blind trial in which they compared the effect of levosimendan to dobutamine in patients that were admitted to a hospital with low-output heart failure and were judged to require hemodynamic monitoring and treatment with an intravenous inotropic agent. In these 203 patients, levosimendan had a consistently better effect than dobutamine on the individual hemodynamic variables at the end of the 24 h treatment period (cardiac output and pulmonary capillary wedge pressure). The change in clinical symptoms like fatigue and dyspnoea were not significantly different, though.
Interestingly, for the first time, the levosimendan group showed lower mortality than in the dobutamine group for up to 180 days. However, it's important to mention its absence of placebo control and its rather small sample size.
Follath et al. Lancet. 2002;360:196–202.
The Big Lumps
The SURVIVE Study
In the SURVIVE study Mebazaa et al. compared the efficacy and safety of intravenous levosimendan or dobutamine in patients hospitalized with acute decompensated heart failure who required inotropic support.
They performed a
randomized, double-blind trial at 75 centers in 9 countries
in which they evaluated
1327 patients hospitalized with acute decompensated heart failure who required inotropic support
They found that
the addition of levosimendan to standard therapy resulted in fewer deaths compared with dobutamine, especially in the first few weeks after treatment
but
Levosimendan did not significantly reduce all-cause mortality at 180 days or affect any secondary clinical outcomes
randomized, double-blind trial at 75 centers in 9 countries
in which they evaluated
1327 patients hospitalized with acute decompensated heart failure who required inotropic support
They found that
the addition of levosimendan to standard therapy resulted in fewer deaths compared with dobutamine, especially in the first few weeks after treatment
but
Levosimendan did not significantly reduce all-cause mortality at 180 days or affect any secondary clinical outcomes
The REVIVE Studies - Heart Failure
In the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy studies (REVIVE I and REVIVE II) the efficacy of levosimendan on symptoms of heart failure during five days after starting a 24h trial drug infusion was assessed.
Each patient's clinical course over 5 days was determined by a composite of the patient's self-assessment of symptoms together with a physician's assessment of the occurrence of clinical deterioration.
The primary endpoint of the study was a new clinical composite endpoint (improvement, unchanged or worse - including death) derived from studies in chronic heart failure and first evaluated in 100 ADHF patients in the REVIVE I pilot study.
In REVIVE II the investigators performed one of the
first large, prospective, randomized, double-blind, controlled trials
in which they evaluated
600 patients admitted at 103 sites in the United States, Australia, and Israel
with
worsening heart failure and dyspnea at rest despite treatment with intravenous diuretics, and left ventricular ejection fraction of < 35% measured within the last year
whereas
patients were randomized to either receive levosimendan for 24h or standard treatment alone
They found that after 5 days
- more patients receiving levosimendan experienced improvement compared with those who were on placebo (19.4% vs 14.6%, respectively, a 33% relative increase; P = .015)
- fewer patients receiving levosimendan worsened compared with patients who were on placebo (19.4% vs 27.2%, respectively), a 29% relative decrease, and
- fewer patients receiving levosimendan required rescue therapy (15.1%) vs placebo (26.2%), a 42% relative decrease.
Among other secondary endpoints, levosimendan improved
B-type natriuretic peptide (BNP) levels, length of hospital stay and dyspnoea at 6 hours
But
mortality at 90 days did not differ significantly between treatment arms (a secondary endpoint) and
the most common treatment-emergent cardiovascular adverse events were more frequent with levosimendan, including hypotension (50% vs 36%), ventricular tachycardia (25% vs 17%), and atrial fibrillation (8% vs 2%).
first large, prospective, randomized, double-blind, controlled trials
in which they evaluated
600 patients admitted at 103 sites in the United States, Australia, and Israel
with
worsening heart failure and dyspnea at rest despite treatment with intravenous diuretics, and left ventricular ejection fraction of < 35% measured within the last year
whereas
patients were randomized to either receive levosimendan for 24h or standard treatment alone
They found that after 5 days
- more patients receiving levosimendan experienced improvement compared with those who were on placebo (19.4% vs 14.6%, respectively, a 33% relative increase; P = .015)
- fewer patients receiving levosimendan worsened compared with patients who were on placebo (19.4% vs 27.2%, respectively), a 29% relative decrease, and
- fewer patients receiving levosimendan required rescue therapy (15.1%) vs placebo (26.2%), a 42% relative decrease.
Among other secondary endpoints, levosimendan improved
B-type natriuretic peptide (BNP) levels, length of hospital stay and dyspnoea at 6 hours
But
mortality at 90 days did not differ significantly between treatment arms (a secondary endpoint) and
the most common treatment-emergent cardiovascular adverse events were more frequent with levosimendan, including hypotension (50% vs 36%), ventricular tachycardia (25% vs 17%), and atrial fibrillation (8% vs 2%).
The LeoPARDS-Trial - Sepsis
In this study investigators wanted to know whether in adult patients who have sepsis the application of levosimendan reduces the incidence and severity of acute organ dysfunction compared with placebo.
In this study investigators wanted to know whether in adult patients who have sepsis the application of levosimendan reduces the incidence and severity of acute organ dysfunction compared with placebo.
They performed a
Randomised, double-blind, placebo-controlled multi-centre trial in 34 general ICUs in the UK
in which they evaluated
516 patients with suspected or confirmed infection and 2 or more SIRS criteria who were dependent on vasopressors for at least four hours to maintain their blood pressure.
They compared
the intravenous infusion of levosimendan or placebo for 24 hours in addition to standard care
and found:
- No significant difference in the daily Sequential Organ Failure Assessment (SOFA) score up to day 28 (primary outcome)
- No statistical difference on death at 28 days, at ICU discharge and hospital discharge (secondary outcome)
- And: The use of levosimendan was associated with more hemodynamic instability, lower mean arterial pressures, therefore more need for noradrenalin at 24h and significantly more supraventricular tachyarrhythmias (all secondary outcomes).
Randomised, double-blind, placebo-controlled multi-centre trial in 34 general ICUs in the UK
in which they evaluated
516 patients with suspected or confirmed infection and 2 or more SIRS criteria who were dependent on vasopressors for at least four hours to maintain their blood pressure.
They compared
the intravenous infusion of levosimendan or placebo for 24 hours in addition to standard care
and found:
- No significant difference in the daily Sequential Organ Failure Assessment (SOFA) score up to day 28 (primary outcome)
- No statistical difference on death at 28 days, at ICU discharge and hospital discharge (secondary outcome)
- And: The use of levosimendan was associated with more hemodynamic instability, lower mean arterial pressures, therefore more need for noradrenalin at 24h and significantly more supraventricular tachyarrhythmias (all secondary outcomes).
The CHEETAH Trial - Cardiac Surgery
The question in CHEETAH was if levosimendan compared to placebo reduces mortality in patients undergoing cardiac surgery with left ventricular dysfunktion.
This time Landoni et al. performed a
Multi-centre, randomised, placebo-controlledand parallel group designed trial
in which they evaluated
506 patients scheduled for cardiac surgery with peri-operative cardiovascular dysfunction
defined as
pre-operative left ventricular ejection fraction (LVEF) < 25%, pre-operative intra-aortic balloon pump (IABP), intra- or post-operative (within 24 hours) IABP or significant inotropic requirement
They compared
Levosimendan infusion continued for up to 48 hours (or until ICU discharge) or placebo
and found
No difference in mortality at thirty 30 days (primary outcome)
And no difference in survival over time, renal replacement therapy, the median duration of mechanical ventilation, the median hospital stay and interruptions due to adverse events (all secondary outcomes).
Any Other Clues?
In contrast to these clinically somewhat discouraging results Shang et al. have published a meta-analysis in 2017 of randomized controlled trials looking at the usage of levosimendan in patients with heart failure, cardiogenic shock and acute coronary syndrome.
They ended up looking at a total of nine studies, most of them low in patient numbers and comparing levosimendan to either placebo or other drugs (dobutamine and enoximone).
In contrast to these clinically somewhat discouraging results Shang et al. have published a meta-analysis in 2017 of randomized controlled trials looking at the usage of levosimendan in patients with heart failure, cardiogenic shock and acute coronary syndrome.
They ended up looking at a total of nine studies, most of them low in patient numbers and comparing levosimendan to either placebo or other drugs (dobutamine and enoximone).
According to these data the authors conclude that levosimendan is associated with reduced total mortality, decreased incidence of worsening HF, and improved hemodynamic outcomes and does not increase the risk of adverse events except for hypotension in patients with HF (including CS) complicating ACS. Thus, levosimendan should be recommended for routine clinical application in these patients.
Am J Cardiovasc Drugs 2017 Dec;17(6):453-463.
According to current evidence
- Levosimendan has interesting mechanisms of action and successfully seems to enhance cardiac output without additional oxygen wasting. This includes decreased right and left ventricular filling pressures, decreased SVR, as well as increases in stroke volume and cardiac index. Also, PCWP is decreased.
- In terms of various patient groups, patients with acute heart failure or acute on chronic heart failure appear to benefit in terms of clinical symptoms, if at all.
- Unfortunately, there is no convincing clinical evidence that levosimendan has any benefit in long term outcomes in terms of mortality.
- And, levosimendan seems to be associated with some potential treatment-emergent cardiovascular adverse events like hypotension, supraventricular and ventricular arrhythmia.
Acute myocardial infarction - It's pain radiating to the right arm we have to worry about!
15/3/2019
It was only back in in 1987 when William Heberdeen (not to confound with William Heberdeen, a London doctor who described the Heberdeen nodes back in the 18th century) published the first description of ischemic chest pain. It was the birth of the classical image of strangling chest pain that occasionally radiates to the left arm, associated with exertion and relieved by rest.
A recent publication in the BMJ shows, that positive troponin levels are found frequently in patients with non-cardiac problems. This finding underlines the importance of good history taking, including the assessment of chest pain (CP) characteristics.
A recent publication in the BMJ shows, that positive troponin levels are found frequently in patients with non-cardiac problems. This finding underlines the importance of good history taking, including the assessment of chest pain (CP) characteristics.
Circulation. 2018;138:e618–e651. (Click image for link to article)
The TRAPID-AMI Study
McCord J et al. have taken a closer look at chest pain and associated symptoms and their association with the diagnosis of acute myocardial infarction. They also analysed these symptoms in relation to the size of the AMI.
They performed an
international, multicenter diagnostic study
in which they evaluated
1282 patients admitted for possible AMI to emergency departments in Europe, the US and Australia
The outcome was
the correlation of symptoms with the diagnosis of AMI and its relation to myocardial infarction size
They found that
1. only 4 symptoms were independently predictive of AMI
- Radiation to the right arm/ shoulder (OR 3.0, CI 1.8-5.0)
- Chest pressure (OR 2.5, CI 1.3-4.6)
- CP worsened by physical activity (OR 1.7, CI 1.2-2.5)
- Radiation to left arm/ shoulder (OR 1.7, CI 1.1-2.4)
2. Patients with more than 1 of the 4 symptoms were more likely to have AMI
- For patients who had all 4 symptoms, 55% had a diagnosis of AMI
3. Patients with larger AMI's were more likely to have
- pulling CP
- pain in the right upper chest (right supramammillary area)
- and right arm/shoulder radiation
They performed an
international, multicenter diagnostic study
in which they evaluated
1282 patients admitted for possible AMI to emergency departments in Europe, the US and Australia
The outcome was
the correlation of symptoms with the diagnosis of AMI and its relation to myocardial infarction size
They found that
1. only 4 symptoms were independently predictive of AMI
- Radiation to the right arm/ shoulder (OR 3.0, CI 1.8-5.0)
- Chest pressure (OR 2.5, CI 1.3-4.6)
- CP worsened by physical activity (OR 1.7, CI 1.2-2.5)
- Radiation to left arm/ shoulder (OR 1.7, CI 1.1-2.4)
2. Patients with more than 1 of the 4 symptoms were more likely to have AMI
- For patients who had all 4 symptoms, 55% had a diagnosis of AMI
3. Patients with larger AMI's were more likely to have
- pulling CP
- pain in the right upper chest (right supramammillary area)
- and right arm/shoulder radiation
- It's time to get rid of the classical image of CP radiating only into the left arm. While this might still be the predominant complaint at presentation, it's the right sided shoulder/ arm pain we should keep a close eye on!
- Chest pain radiating to the right shoulder/ arm is more predicitive of myocardial infarction than left sided chest pain
- And remember: a positive Troponin alone does not fullfill the diagnostic criteria of AMI!
Crit Pathw Cardiol. 2019 Mar;18(1):10-15.
Top Ten Websites in Critical Care Medicine Education
The Journal of Intensive Care Medicine has recently published a review of websites providing educational content that is part of the Free Open Access Meducation (FOAMed) movement. The authors have searched the web for critical care medicine education websites and have identified 97 sites they consider relevant for critical care.
These websites were then reviewed and evaluated using the Critical Care Medical Education Website Quality Evaluation Tool (CCMEWQET). They were then split up into three tertiles according to their score.
Congratulations to the Top Ten websites that indeed provide excellent educational information freely accessible.
Oh, and by the way we might mention that our small site Crit.Cloud has been considered among 96 other as relavant in this field and has ended up in the middle tertile with its ranking. 🙃
A big thank you to the authors of this paper for their excellent work and for providing us with an updated list of websites worth taking a closer look! We are delighted to follow their wish by sharing the table of these websites.
Wolbrink TA et al. J Intensive Care Med. 2018 Jan;34(1):3-16
Full List of all Website Reviewed (Click on a table enlarge)
Central venous lines a commonly used in critical care and normally don't cause too many problems. They are though associated with potentially severe complications like infection, thrombosis, occlusion, bleed and of course pneumothorax on insertion. Although the usage of ultrasound guidance minimises the risk of the latter, there remains a restriction risk of this happening, giving you the challenge to solve this problem professionally.
The Case
A 67-year old lady needed the insertion of a central venous catheter during surgery, which the anaesthetist performed with the aid of ultrasound but of course under aggravated conditions. When brought into the critical care unit postoperatively she presented with no audible breathing sound on the right side of her chest. An ultrasound (US) of the right lung showed no visible pleural gliding, and in M-mode only 'sea' but no 'beach' or 'sand'.
Left lung: Beach, Sea and Sky: No pneumothorax!
Right lung: No Beach (no sand): Suggests pneumothorax!
To estimate the extent of the pneumothorax, we performed a pa chest x-ray (CR), which confirmed the diagnosis. The image showed an apical interpleural distance of 3cm and laterally of 2-3cm.
To estimate the extent of the pneumothorax, we performed a pa chest x-ray (CR), which confirmed the diagnosis. The image showed an apical interpleural distance of 3cm and laterally of 2-3cm.
How often does this happen? Could I have prevented this complication? What would you do in this situation? To answer these and some other questions we performed a quick review of current literature and provide a short review.
Are iatrogenic pneumothoraces common?
It's a fact: Iatrogenic injuries are an inevitable part of medicine. Emergent procedures performed in the emergency department (ED) present a higher risk for iatrogenic injury than in more controlled settings (Swain et al., 2005; Mort, 2004). This fact implies that you should NEVER perform a procedure if you cannot handle the potential complications. A procedural error followed by mismanagement increases the likelihood of morbidity and mortality immensely.
The incidence in the literature varies from 0 to 6% (numbers are higher in emergencies), bearing in mind, that depending on the control method used (US, CR or none), some are just not diagnosed. Subclavian vein insertion has been reported to have a higher incidence of pneumothorax than internal jugular vein insertion.
The incidence in the literature varies from 0 to 6% (numbers are higher in emergencies), bearing in mind, that depending on the control method used (US, CR or none), some are just not diagnosed. Subclavian vein insertion has been reported to have a higher incidence of pneumothorax than internal jugular vein insertion.
What can I do to prevent iatrogenic pneumothoraces?
- Make sure that there is an indication for central venous access (e.g. vasopressors in low to moderate doses are no absolute indication, PulmCC: Are central lines really needed for vasopressor infusions?)
- Use a standardized method of CVC insertion in your unit or institution
- Insertion by experienced physician (performing more than 50 CVC insertion a year) or at least his assistance has proved to lower the risk of pneumothorax
- The use of ultrasound during CVC catheterization reduces the time required for insertion and the rate of mechanical complications
- Use a standardized method of CVC insertion in your unit or institution
- Insertion by experienced physician (performing more than 50 CVC insertion a year) or at least his assistance has proved to lower the risk of pneumothorax
- The use of ultrasound during CVC catheterization reduces the time required for insertion and the rate of mechanical complications
How do I diagnose a pneumothorax
Iatrogenic pneumothorax might not cause any clinical symptoms, especially in the young and otherwise healthy patient. Symptoms might include chest pain (sometimes radiating to the ipsilateral shoulder), shortness of breath (to life-threatening respiratory distress) and less commonly cough, anxiety or malaise.
On examination, you might find tachypnoea, asymmetrical lung expansion, unilaterally decreased breath sounds. Cardiovascular findings might include tachycardia, hypotension, pulsus paradoxus and jugular venous distension (often present in tension pneumothorax). Subcutaneous emphysema and tracheal deviation might occur occasionally.
A definite diagnosis is made by performing chest radiography (CR), CT-scan or bedside ultrasonography (US). Supine chest radiographs are unreliable in making the diagnosis of pneumothorax, with a sensitivity value of 36%. US is more sensitive than supine CR and as sensitive as CT in the detection of pneumothoraces. Performance of US for the detection of pneumothorax is excellent and is superior to supine CR. Considering the ease of access and the outstanding clinical performance of US (numerous studies have described near 100% sensitivity and 90% to 95% specificity if a thorough examination is performed), current studies support the routine use of US for the detection of pneumothorax.
- Clinical signs are unspecific and might not be present
- Ultrasonography is the first choice for the detection of pneumothorax
- For a general evaluation of the size of a pneumothorax, an erect chest x-ray in inspiration is recommended
- CT scans are only recommended for uncertain or complex cases
On examination, you might find tachypnoea, asymmetrical lung expansion, unilaterally decreased breath sounds. Cardiovascular findings might include tachycardia, hypotension, pulsus paradoxus and jugular venous distension (often present in tension pneumothorax). Subcutaneous emphysema and tracheal deviation might occur occasionally.
A definite diagnosis is made by performing chest radiography (CR), CT-scan or bedside ultrasonography (US). Supine chest radiographs are unreliable in making the diagnosis of pneumothorax, with a sensitivity value of 36%. US is more sensitive than supine CR and as sensitive as CT in the detection of pneumothoraces. Performance of US for the detection of pneumothorax is excellent and is superior to supine CR. Considering the ease of access and the outstanding clinical performance of US (numerous studies have described near 100% sensitivity and 90% to 95% specificity if a thorough examination is performed), current studies support the routine use of US for the detection of pneumothorax.
- Clinical signs are unspecific and might not be present
- Ultrasonography is the first choice for the detection of pneumothorax
- For a general evaluation of the size of a pneumothorax, an erect chest x-ray in inspiration is recommended
- CT scans are only recommended for uncertain or complex cases
Does every central line need a chest x-ray after insertion?
CR of supine patients is not sensitive enough to identify hidden pneumothorax because the air initially dissipates within the nondependent and medial parts of the chest and therefore can be invisible on supine radiographs. Even upright CR can be challenging and unreliable. Also, CR is often performed immediately after CVC insertion and it is therefore possible that there is not enough time for the development of a pneumothorax large enough to be identified.
- Routine CR after central line insertion is unreliable and not necessary: It's an inefficient screening tool!
- Current evidence supports the use of US to exclude iatrogenic pneumothorax
- Routine CR after central line insertion is unreliable and not necessary: It's an inefficient screening tool!
- Current evidence supports the use of US to exclude iatrogenic pneumothorax
How do I treat an iatrogenic pneumothorax?
If a pneumothorax occurs during the insertion of a central line urgent action might not be necessary. If asymptomatic, you might proceed with the central line insertion when the patient is in urgent need.
- If signs of a tension pneumothorax arise, a simple needle decompression or urgent chest drain is life-saving and allows for a continued controlled attempt of the central line on the same side (you can’t cause a pneumothorax twice).
- Never attempt a central line insertion on the opposite side to avoid bilateral iatrogenic complications!
- In the setting of iatrogenic pneumothorax the BTS guidelines on the management of spontaneous pneumothorax can be applied:
- If signs of a tension pneumothorax arise, a simple needle decompression or urgent chest drain is life-saving and allows for a continued controlled attempt of the central line on the same side (you can’t cause a pneumothorax twice).
- Never attempt a central line insertion on the opposite side to avoid bilateral iatrogenic complications!
- In the setting of iatrogenic pneumothorax the BTS guidelines on the management of spontaneous pneumothorax can be applied:
- Remember: If the inter-pleural space on CR is less than 2cm (some allow 3cm as an upper limit) and the patient remains asymptomatic, conservative treatment is appropriate!
- Apply nasal oxygen 3-5L/min (see below)
- A follow up chest x-rax after 12-24 hours is advisable.
Did you know?
When no supplemental oxygen is applied air is reabsorbed spontaneously by 1.25% of pneumothorax size per day. Oxygen administration at 3 L/min nasal canula or higher flow treats possible hypoxemia and is associated with a fourfold increase in the rate of pleural air absorption compared with room air alone.
Got interested? Get more info here:
Pneumothorax as a complication of central venous catheter insertion, N. Tsotsolis et al. Ann Transl Med. 2015 Mar; 3(3): 40. OPEN ACCESS
Management of spontaneous pneumothorax: British Thoracic Society pleural disease guideline 2010, A. MacDuff et al. Thorax. 2010 Aug. OPEN ACCESS
Ding W. et al. Diagnosis of pneumothorax by radiography and ultrasonography: a meta-analysis. Chest. 2011 Oct;140(4):859-866.
Contou D et al. Small-bore catheter versus chest tube drainage for pneumothorax. Am J Emerg Med. 2012 Oct. 30 (8):1407-13.
Rami A. et al. Iatrogenic emergency medicine procedure complications and associated trouble-shooting strategies: A narrative review: https://doi.org/10.1108/IJHCQA-08-2017-0157 OPEN ACCESS
Just recently a 75-year-old gentleman was admitted to our unit as he remained unresponsive after short procedural sedation with Propofol. Although he was hemodynamically stable and showed proper spontaneous breathing at any time, the intervention team was concerned about his condition.
On arrival to our ICU, the patient was noted to be still unresponsive. He showed no reaction to painful stimulation. The Pupils were rather wide, but symmetrical in size and showed a prompt response to light. Brain stem reflexes were present and peripheral reflexes were triggerable. His breathing pattern was regular, and saturation levels were above 96% on room air. A blood gas analysis showed a normal pH and normal CO2-levels.
As usual, the common reflexes started to kick in, and some suggested to go for a CT-scan of his head to out-rule some significant complications. Luckily enough, close observation revealed some slow improvement of his alertness, and we considered the possible diagnosis of a central anticholinergic syndrome (CAS).
After the application of 1mg of physostigmine (2x0.5mg) intravenously the patient almost promptly awoke and had an uneventful stay on our unit.
This case just reminded me of these many patients in anaesthesia that inexplicably show delayed awakening after sedation or a general anaesthetic.
In fact, it is estimated that the incidence of central anticholinergic syndrome is around 8- 12 % following general anaesthetic and lesser with regional anaesthesia.
On arrival to our ICU, the patient was noted to be still unresponsive. He showed no reaction to painful stimulation. The Pupils were rather wide, but symmetrical in size and showed a prompt response to light. Brain stem reflexes were present and peripheral reflexes were triggerable. His breathing pattern was regular, and saturation levels were above 96% on room air. A blood gas analysis showed a normal pH and normal CO2-levels.
As usual, the common reflexes started to kick in, and some suggested to go for a CT-scan of his head to out-rule some significant complications. Luckily enough, close observation revealed some slow improvement of his alertness, and we considered the possible diagnosis of a central anticholinergic syndrome (CAS).
After the application of 1mg of physostigmine (2x0.5mg) intravenously the patient almost promptly awoke and had an uneventful stay on our unit.
This case just reminded me of these many patients in anaesthesia that inexplicably show delayed awakening after sedation or a general anaesthetic.
In fact, it is estimated that the incidence of central anticholinergic syndrome is around 8- 12 % following general anaesthetic and lesser with regional anaesthesia.
What is a Central Anticholinergic Syndrome?
Classically the central anticholinergic syndrome (CAS) describes a condition where a substance causes a competitive antagonism of acetylcholine (ACh) at peripheral and central muscarinic receptors. Initially, these were plants containing atropine, hyoscyamine and scopolamine.
There are four muscarinic receptors:
- M1 mainly in the central nervous system (responsible for delirium when antagonised)
- M2 in the brain and heart
- M3 in the salivary glands and
- M4 in the brain and lungs
The PERIPHERAL SYNDROME presents with:
- Dry mouth
- Difficulty swallowing (lack of saliva)
- Photophobia and blurred vision (due to dilated pupils)
- Dry skin, fever
- Reduced bowel sounds and urinary retention
The CENTRAL SYNDROME presents with:
- Agitation, agitated delirium, visual and auditory hallucinations
- Hypoactive delirium may also occur, this seems to be more common though in the postoperative setting
The clinical diagnosis of a CAS is more straightforward when typical peripheral symptoms accompany central signs.
The Problem with the "Silent" Postoperative CAS
The clinical diagnosis of a CAS is often straight forward when typical central symptoms accompany peripheral symptoms. The problems are patients in the postoperative setting, in which the patient often presents with somewhat atypical central symptoms and often minimal or even no peripheral symptoms at all.
Especially in this setting, the anticholinergic syndrome may be accompanied by sedation or coma. The mechanisms causative for this phenomenon are not well understood but might include greater tolerance at peripheral receptors, longer persistence at central receptors or greater CNS susceptibility due to age or disease.
Postoperative CAS is often associated with atypical central symptoms and minimal or even no peripheral signs at all! Sedation and coma are often observed in this setting.
What Drugs Cause CAS?
Common anticholinergics agents should be more accurately referred to as antimuscarinics, as these agents do not generally block nicotinic receptors.
A. H. Dawson, Br J Clin Pharmacol, Nov 2015
The Problem is that many currently used drugs in anaesthesia and critical care are also known to cause this syndrome.
This includes:
Benzodiazepines, opioids, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and volatile inhaled anaesthetics!
How Can I Diagnose a "Silent" Postoperative CAS?
The fact that postoperative CAS often lacks the presence of peripheral symptoms makes the diagnosis challenging. The different presentation of the syndrome ranging from somnolence, confusion, amnesia, delayed recovery, stupor, coma to agitation, hallucinations, dysarthria, ataxia, delirium makes it difficult to diagnose accurately.
It is, therefore, a diagnosis of exclusion! The most helpful tool you have is physostigmine!
The prompt arousal of a patient after the application of intravenous physostigmine is highly suggestive of a postoperative central anticholinergic syndrome.
How to Use Physostigmine
When dealing with prolonged somnolence or unexplained agitation following any form of anaesthesia, make sure to check and monitor vital signs and provide basic or advanced life support if necessary.
Exclude common causes first (e.g. overhang of sedatives or opioids, persistent muscular paralysis, hypoxemia, hypercapnia, hypoglycemia and other).
If common causes can be excluded and CAS is a probable diagnosis, you should consider the application of intravenous physostigmine.
Physostigmine in recommended doses is considered safe! Possible adverse effects are considered unlikely. Studies found cholinergic symptoms sometimes to be mild, and these adverse effects are more an indication of probable excessive doses rather than an established safety concern.
For postoperative CAS a dose of 1mg of physostigmine i/v is recommended.
This dose can be divided into two doses of 0.5mg i/v if required.
The maximum dose recommended in this setting is 2mg i/v.
Beware: You are giving Physostigmine Salicylat - Do not give to patients with aspirin allergy!
Updated 28/01/2019
While this website concentrates on finding relevant publications from the world of Critical Care, there are always papers from other fields that attract our attention.
Recently, a remarkable detail from a publication of an even more noteworthy journal has been brought to our notice. I admit I rarely read articles on 'Nature', but this article is worth a very close look after all.
Chiou L. et al. have published an article about a noninvasive genomic sequencing of populations from faeces in this years January issue of Scientific Reports of 'Nature'. In this article, they deal with the problem that it is difficult to obtain high-quality samples for genomic studies from wild animals. They, therefore, describe a cost-effective method for enriching host DNA from noninvasive faecal samples.
And in fact, it is worthwhile to have a closer look at the faeces sample in this article as Nature has placed a portrait of Mr Trump in a rather delicate position.
While this website concentrates on finding relevant publications from the world of Critical Care, there are always papers from other fields that attract our attention.
Recently, a remarkable detail from a publication of an even more noteworthy journal has been brought to our notice. I admit I rarely read articles on 'Nature', but this article is worth a very close look after all.
Chiou L. et al. have published an article about a noninvasive genomic sequencing of populations from faeces in this years January issue of Scientific Reports of 'Nature'. In this article, they deal with the problem that it is difficult to obtain high-quality samples for genomic studies from wild animals. They, therefore, describe a cost-effective method for enriching host DNA from noninvasive faecal samples.
And in fact, it is worthwhile to have a closer look at the faeces sample in this article as Nature has placed a portrait of Mr Trump in a rather delicate position.
Finding the hidden Trump-Portrait, here's how:
Update 28/01/2019: The authors have reacted and changed the resolution of the image so that a closer zoom is no longer possible. Following instructions refers to the previous publication.
1. Open the article in pubmed (just to proof, it's no fake news):
Chiou KL et al. Scientific Reports, 2018 January 31: Methylation-based enrichement facilitates low-cost, noninvasive genomic scale sequencing of populations from feces
2. It's OPEN ACCESS! Open the article via the full text links on the top right.
3. Download the pdf version of the article.
4. Go to page 3, figure 1. Spot the heap of feces right behind the pavian?
5. Zoom in on that heap of feces... zoom in closer... even closer!
This publication impressively demonstrates the interdependence of science and politics.
Remember, sometimes the unexpected lies in the detail.
Did the editors of Nature actually realise this?
Update 28/01/2019: Well, obviously they now have!
OPEN ACCESS: Chiou KL et al. Scientific Reports 2018 January 31: Methylation-based enrichement facilitates low-cost, noninvasive genomic scale sequencing of populations from feces
Anticoagulated patients are common, and the amount of available oral anticoagulants is becoming more diverse and confusing. Anticoagulation is the cornerstone in the treatment of thrombosis and thromboembolic complications in a variety of diseases. Lixiana, Pradaxa, Eliquis and Xarelto are some of these pretty-sounding drugs that many doctors know but find it difficult to keep up.
So if you work in an emergency room, anaesthesia or intensive care, there's a good chance you will be facing an anticoagulant patient with potentially critical bleeding that could require urgent treatment... And this leaves you with the following questions:
- What is a critical bleed (apart from obvious massive bleeding)? Does this bleeding need imminent reversal?
- Do I need any laboratory testing before?
- What treatment should I actually give the patient?
If you do not have a guideline in your institution, it may be time to create one, and the following publication is indeed very useful for this purpose!
The 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants very nicely summarises current evidence and expert opinion on these issues. But the very best are their excellent figures, providing all the answers you need: simple and very understandable!
So if you work in an emergency room, anaesthesia or intensive care, there's a good chance you will be facing an anticoagulant patient with potentially critical bleeding that could require urgent treatment... And this leaves you with the following questions:
- What is a critical bleed (apart from obvious massive bleeding)? Does this bleeding need imminent reversal?
- Do I need any laboratory testing before?
- What treatment should I actually give the patient?
If you do not have a guideline in your institution, it may be time to create one, and the following publication is indeed very useful for this purpose!
The 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants very nicely summarises current evidence and expert opinion on these issues. But the very best are their excellent figures, providing all the answers you need: simple and very understandable!
What is a Critical Bleeding?
Do I Need any Laboratory Tests Before?
What Treatment Should I Give the Patient for Reversal?
Just recently our ICU team was called to the wards to look at a 74-year-old gentleman with sudden shortness of breath and low peripheral saturation. He was known to suffer from hypertensive heart disease and now presented with acute pulmonary oedema. After giving oxygen over a non-rebreathing mask, he was administered furosemide (Lasix) intravenously and brought to the unit for non-invasive ventilation.
Interestingly a discussion started on whether giving Lasix as a first line agent in the acute setting of pulmonary oedema is beneficial or not. A quick look into to current literature gave no clear answer and reading further into the topic revealed unusual properties of Lasix we hadn't been really aware of so far. We all use and love Lasix, but do we really know the drug?
The Beginning of Lasix
Furosemide (sometimes also called frusemide) was first developed by 'Farbwerke Hoechst AG' in Frankfurt am Main, Germany, a company that was founded back in the year 1863. Karl Stürm, Walter Siedel and Rüdi Weyer set the basis with the invention of N-substituted-3-Carboxy-6-Halo-Sulfanilamide, and it's derivates, one of them being furosemide. The researchers soon noticed its saluretic (sodium Na, potassium K and chloride Cl) and diuretic effect in almost equivalent proportions. As these substances did not cause any acidosis nor alkalosis, they suggested their future use for the treatment of oedema and hypertension.
Interestingly a discussion started on whether giving Lasix as a first line agent in the acute setting of pulmonary oedema is beneficial or not. A quick look into to current literature gave no clear answer and reading further into the topic revealed unusual properties of Lasix we hadn't been really aware of so far. We all use and love Lasix, but do we really know the drug?
The Beginning of Lasix
Furosemide (sometimes also called frusemide) was first developed by 'Farbwerke Hoechst AG' in Frankfurt am Main, Germany, a company that was founded back in the year 1863. Karl Stürm, Walter Siedel and Rüdi Weyer set the basis with the invention of N-substituted-3-Carboxy-6-Halo-Sulfanilamide, and it's derivates, one of them being furosemide. The researchers soon noticed its saluretic (sodium Na, potassium K and chloride Cl) and diuretic effect in almost equivalent proportions. As these substances did not cause any acidosis nor alkalosis, they suggested their future use for the treatment of oedema and hypertension.
The Naming of Furosemide
Researchers soon noticed that the diuretic effect of furosemide lasted for about 6 hours... 'LAsts for SIX hours'... and therefore gave it the name: LASIX!
What is Furosemide
Furosemide is an organic anion from the group of loop diuretics (as are bumetanide and torasemide) and is sold under the brand name of Lasix©. Its indications are for the treatment of oedema due to heart or liver disease as well as kidney disease. It is also used for the treatment of mild or moderate hypertension. Furosemide has become one of the cornerstones in the treatment of heart failure.
Researchers soon noticed that the diuretic effect of furosemide lasted for about 6 hours... 'LAsts for SIX hours'... and therefore gave it the name: LASIX!
What is Furosemide
Furosemide is an organic anion from the group of loop diuretics (as are bumetanide and torasemide) and is sold under the brand name of Lasix©. Its indications are for the treatment of oedema due to heart or liver disease as well as kidney disease. It is also used for the treatment of mild or moderate hypertension. Furosemide has become one of the cornerstones in the treatment of heart failure.
How does it work?
Furosemide can be applied by oral intake as a tablet or as an intravenous injection. Once in the bloodstream, it is predominantly bound to proteins (>90%).
Loop diuretics do not undergo glomerular filtration. In fact, they pass the glomerulus and are actively secreted across proximal tubular cells by organic anion transporters and the multidrug resistance-associated protein 4 (area A). It is important to know that non-steroidal anti-inflammatory drugs (NSAID) and endogenous uremic anions compete with this loop diuretic secretion and can cause 'diuretic resistance'.
Once loop diuretics have reached the tubular system, they bind to sodium-potassium-chloride co-transporters (NKCC2) in the ascending limb of the loop of Henle and block the reabsorption of these ions directly (area B). Further down at the macula densa they inhibit the same co-transporter (area B) thereby stimulating renin secretion and inhibiting tubuloglomerular feedback. This results in preserved glomerular filtration despite increased salt delivery to the macula densa. All this finally results in the loss of sodium, chloride and potassium and therefore loss of water.
Furosemide can be applied by oral intake as a tablet or as an intravenous injection. Once in the bloodstream, it is predominantly bound to proteins (>90%).
Loop diuretics do not undergo glomerular filtration. In fact, they pass the glomerulus and are actively secreted across proximal tubular cells by organic anion transporters and the multidrug resistance-associated protein 4 (area A). It is important to know that non-steroidal anti-inflammatory drugs (NSAID) and endogenous uremic anions compete with this loop diuretic secretion and can cause 'diuretic resistance'.
Once loop diuretics have reached the tubular system, they bind to sodium-potassium-chloride co-transporters (NKCC2) in the ascending limb of the loop of Henle and block the reabsorption of these ions directly (area B). Further down at the macula densa they inhibit the same co-transporter (area B) thereby stimulating renin secretion and inhibiting tubuloglomerular feedback. This results in preserved glomerular filtration despite increased salt delivery to the macula densa. All this finally results in the loss of sodium, chloride and potassium and therefore loss of water.
Other Effects
Furosemide also interacts with other sodium-potassium-chloride co-transporters (NKCC1) elsewhere in the body:
- Blocking NKCC1 in the ear probably explains the ototoxicity of loop diuretics
- Blocking NKCC1 in smooth muscle cells causes vasodilation
- Blocking NKCC1 in the afferent arteriole and near the macula densa elevates renin secretion and the generation of angiotensin II
These complex interactions on haemodynamics explain that the net response in each patient might be different. On the one hand, loop diuretics dilate blood vessels directly and increase the level of vasodilatory prostaglandins. On the other hand, some of these effects counteract each other making it difficult to predict which effect will finally predominate.
Many studies have looked closer into the vasoactive properties of furosemide. Current evidence indicates that it has a systemic venodilator effect which actually reduced preload acutely. The same investigators found a reduction in the right atrial pressure and the pulmonary capillary wedge pressure, presumably reflecting the systemic venodilator effect of furosemide.
While the acute venodilator effect may be beneficial to the failing heart, its action on arteries might be detrimental. Several studies have shown that in patients with chronic heart failure furosemide causes arterial vasoconstriction. Also, there is one study showing that pulmonary vascular resistance in healthy volunteers rose significantly.
Francis GS et al. described how the administration of furosemide actually led to decreased LV function, increased LV filling pressures, increases in MAP, SVR, plasma renin activity, and plasma noradrenaline levels.
Beneficial venodilator response predominates over arterial vasoconstriction in patients with (1) myocardial infarction and (2) salt depleted volunteers.
Venous relaxant effect has not been demonstrated in patients with chronic heart failure. In this setting detrimental arterial vasoconstriction seems to predominate.
Pardeep S et al. Br J Clin Pharmacol. 2000 Jul; 50(1): 9–13.
Francis GS et al. Ann Int Med 1985; 103(1): 1-6.
Pharmacological Properties
Administered furosemide orally has a limited and highly variable bioavailability. The diuretic effect starts within the first hour, and the duration of action is around 6 hours (4-8 hours). Injected furosemide intravenously is approximately twice as potent on a per-milligramme basis as oral doses.
In acute decompensated heart failure sodium retention becomes more avid and higher peak levels might be required to become more effective. This can be achieved by giving furosemide intravenously.
Once a loop diuretic is administered, the excretion of sodium chloride is increased for several hours. This is then followed by a period of very low sodium excretion resulting in a so-called 'post-diuretic retention'.
How to use Furosemide for Acute Decompensated Heart Failure (ADHF)
So far for the basics of furosemide, but what about its usage for acutely decompensated heart failure? Should furosemide be given as soon as possible or not?
The 2013 ACCF/AHA guidelines for the management of patients with heart failure give diuretics a class I recommendation. The evidence behind these recommendations though is level B or level C only! So these recommendations are not really helpful to answer this question.
The authors in UpToDate® mention diuretics directly after the use of oxygen. For patients with evidence of volume overload their recommendation is to give loop diuretics immediately (Grade 1B) as there is evidence that in this setting this may improve outcomes. They also suggest that patients with ADHF usually are volume overloaded, therefore indicating that most patients should receive diuretics ASAP.
The only exception they mention where some delay in inducing diuresis might be required is in patients with severe hypotension or cardiogenic shock.
There is reasonable doubt that patients with ADHF are usually volume overloaded, as suggested by UpToDate®. Zile MR et al. demonstrated that while most patients with acute pulmonary oedema have increased filling pressures, most did not have significant increases from their dry weight on presentation! Fallick et al. actually argue that it isn't fluid gain but rather shift in fluids from other compartments, mainly shift from the splanchnic circulation, which usually is very compliant.
And as mentioned above, there is evidence that giving a straight shot of furosemide might actually influence haemodynamics negatively in different ways (decreased LV function, increased LV filling pressures, increases in MAP, SVR, plasma renin activity and plasma noradrenaline levels).
In conclusion there is no straight forward answer to this question, but I would put it down as follows:
Furosemide also interacts with other sodium-potassium-chloride co-transporters (NKCC1) elsewhere in the body:
- Blocking NKCC1 in the ear probably explains the ototoxicity of loop diuretics
- Blocking NKCC1 in smooth muscle cells causes vasodilation
- Blocking NKCC1 in the afferent arteriole and near the macula densa elevates renin secretion and the generation of angiotensin II
These complex interactions on haemodynamics explain that the net response in each patient might be different. On the one hand, loop diuretics dilate blood vessels directly and increase the level of vasodilatory prostaglandins. On the other hand, some of these effects counteract each other making it difficult to predict which effect will finally predominate.
Many studies have looked closer into the vasoactive properties of furosemide. Current evidence indicates that it has a systemic venodilator effect which actually reduced preload acutely. The same investigators found a reduction in the right atrial pressure and the pulmonary capillary wedge pressure, presumably reflecting the systemic venodilator effect of furosemide.
While the acute venodilator effect may be beneficial to the failing heart, its action on arteries might be detrimental. Several studies have shown that in patients with chronic heart failure furosemide causes arterial vasoconstriction. Also, there is one study showing that pulmonary vascular resistance in healthy volunteers rose significantly.
Francis GS et al. described how the administration of furosemide actually led to decreased LV function, increased LV filling pressures, increases in MAP, SVR, plasma renin activity, and plasma noradrenaline levels.
Beneficial venodilator response predominates over arterial vasoconstriction in patients with (1) myocardial infarction and (2) salt depleted volunteers.
Venous relaxant effect has not been demonstrated in patients with chronic heart failure. In this setting detrimental arterial vasoconstriction seems to predominate.
Pardeep S et al. Br J Clin Pharmacol. 2000 Jul; 50(1): 9–13.
Francis GS et al. Ann Int Med 1985; 103(1): 1-6.
Pharmacological Properties
Administered furosemide orally has a limited and highly variable bioavailability. The diuretic effect starts within the first hour, and the duration of action is around 6 hours (4-8 hours). Injected furosemide intravenously is approximately twice as potent on a per-milligramme basis as oral doses.
In acute decompensated heart failure sodium retention becomes more avid and higher peak levels might be required to become more effective. This can be achieved by giving furosemide intravenously.
Once a loop diuretic is administered, the excretion of sodium chloride is increased for several hours. This is then followed by a period of very low sodium excretion resulting in a so-called 'post-diuretic retention'.
How to use Furosemide for Acute Decompensated Heart Failure (ADHF)
So far for the basics of furosemide, but what about its usage for acutely decompensated heart failure? Should furosemide be given as soon as possible or not?
The 2013 ACCF/AHA guidelines for the management of patients with heart failure give diuretics a class I recommendation. The evidence behind these recommendations though is level B or level C only! So these recommendations are not really helpful to answer this question.
The authors in UpToDate® mention diuretics directly after the use of oxygen. For patients with evidence of volume overload their recommendation is to give loop diuretics immediately (Grade 1B) as there is evidence that in this setting this may improve outcomes. They also suggest that patients with ADHF usually are volume overloaded, therefore indicating that most patients should receive diuretics ASAP.
The only exception they mention where some delay in inducing diuresis might be required is in patients with severe hypotension or cardiogenic shock.
There is reasonable doubt that patients with ADHF are usually volume overloaded, as suggested by UpToDate®. Zile MR et al. demonstrated that while most patients with acute pulmonary oedema have increased filling pressures, most did not have significant increases from their dry weight on presentation! Fallick et al. actually argue that it isn't fluid gain but rather shift in fluids from other compartments, mainly shift from the splanchnic circulation, which usually is very compliant.
And as mentioned above, there is evidence that giving a straight shot of furosemide might actually influence haemodynamics negatively in different ways (decreased LV function, increased LV filling pressures, increases in MAP, SVR, plasma renin activity and plasma noradrenaline levels).
In conclusion there is no straight forward answer to this question, but I would put it down as follows:
- Furosemide should not be routinely used for the immediate treatment of acute decompensated heart failure (ADHF)/ acute pulmonary oedema
- However, in patients with evidence of volume overload the administration of early furosemide (preferentially given as an intravenous bolus) seems beneficial and improves outcome. But beware, most patients are not volume overloaded!
- In urgent situations the focus should be on early non-invasive ventilation and the administration of nitroglycerin!
David H et al. N Engl J Med 2017;377:1964-75.
Wilson S et al., UpToDate.com 2018
WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013; 128:e240.
Zile MR, Bennett TD, St John Sutton M, et al. Circulation 2008 Sep 30;118(14):1433-41
Fallick C et al. Circ Heart Fail 2011; 4: 669-75.
Wilson S et al., UpToDate.com 2018
WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013; 128:e240.
Zile MR, Bennett TD, St John Sutton M, et al. Circulation 2008 Sep 30;118(14):1433-41
Fallick C et al. Circ Heart Fail 2011; 4: 669-75.
Clinicians are confronted every day with a growing number pacemakers (PMs), implantable cardioverter-defibrillators (ICDs) and implantable loop recorders (ILRs). Collectively these devices are sub summarised as cardiac rhythm management devices (CRMDs). Identification of these devices is simple as long a the patient can present an ID card or some other form of identification. This can become challenging especially in emergencies where such information might not be accessible, and interrogation of the pacemaker becomes a problem.
Using the wrong manufacturer-specific device programmer causes a delay in diagnostic and treatment and can be relevant in these situations.
Techniques to identify a CRMD are following:
- Patient's ID card
- Medical records
- Manufacturers' patient registries (All CRMD manufacturers keep their own in-house registry of patients implanted with their devices and provide 24-hour telephone technical support
- Device specific radiopaque alphanumeric codes (ANC)
All these identification techniques have their problems in clinical practice, and so far no other method or algorithm was available to help out in such a dilemma. Sony Jacob et al. have therefore developed and validated the so-called
Cardiac Rhythm Device Identification Algorithm using X-rays (CaRDIA-X, see below)
The study participants using this algorithm showed an overall accuracy of 96.9%. This study was published in 2011 but only now caught our attention.
Using the wrong manufacturer-specific device programmer causes a delay in diagnostic and treatment and can be relevant in these situations.
Techniques to identify a CRMD are following:
- Patient's ID card
- Medical records
- Manufacturers' patient registries (All CRMD manufacturers keep their own in-house registry of patients implanted with their devices and provide 24-hour telephone technical support
- Device specific radiopaque alphanumeric codes (ANC)
All these identification techniques have their problems in clinical practice, and so far no other method or algorithm was available to help out in such a dilemma. Sony Jacob et al. have therefore developed and validated the so-called
Cardiac Rhythm Device Identification Algorithm using X-rays (CaRDIA-X, see below)
The study participants using this algorithm showed an overall accuracy of 96.9%. This study was published in 2011 but only now caught our attention.
We have tried this algorithm on a few X-rays ourselves and came to the conclusion:
Using the chart is a little challenge itself, but very helpful in most cases! Certainly worth keeping in mind!
Jacob S et al. Heart Rhythm. 2011 Jun;8(6):915-22.
Using the chart is a little challenge itself, but very helpful in most cases! Certainly worth keeping in mind!
Jacob S et al. Heart Rhythm. 2011 Jun;8(6):915-22.
We just had the discussion again and finally found a good and solid answer to it:
A 19 year old male was transferred to our unit from casualty with a GCS of 10 (E2, V3, M5) secondary to a little bit of... to many drinks. As he was found lying on the ground with no company an unwitnessed fall was considered and a rigid collar applied by paramedics. A c-spine CT-scan in the hospital showed no abnormalities and the patient was transferred to ICU for further treatment... with the rigid collar still in place!
The question soon arose whether it is safe to remove a rigid collar in the intoxicated and dazed patient after a normal c-spine scan or not. Some argued that the patient should also be examined clinically once sober in order to safely evaluate and clear the spine. As always by the way: The rigid collar was removed in ICU and no further problems evolved.
At that time we just knew it is safe to do so but now we seem to get some excellent evidence supporting this procedure.
Martin et al. have just published a
A 19 year old male was transferred to our unit from casualty with a GCS of 10 (E2, V3, M5) secondary to a little bit of... to many drinks. As he was found lying on the ground with no company an unwitnessed fall was considered and a rigid collar applied by paramedics. A c-spine CT-scan in the hospital showed no abnormalities and the patient was transferred to ICU for further treatment... with the rigid collar still in place!
The question soon arose whether it is safe to remove a rigid collar in the intoxicated and dazed patient after a normal c-spine scan or not. Some argued that the patient should also be examined clinically once sober in order to safely evaluate and clear the spine. As always by the way: The rigid collar was removed in ICU and no further problems evolved.
At that time we just knew it is safe to do so but now we seem to get some excellent evidence supporting this procedure.
Martin et al. have just published a
prospective multicenter study at 17 centers
in which they analyzed
10191 trauma patients that underwent CT of the c-spine during their primary evaluation (67% male, 83% car accidents or falls, mean ISS 11)
They found that
the intoxicated cohort had a lower incidence of c-spine injuries
and that
c-spine CT had a sensitivity of 94%, a specifity of 99.5% and a negative predicitve value of 99.9%!
in which they analyzed
10191 trauma patients that underwent CT of the c-spine during their primary evaluation (67% male, 83% car accidents or falls, mean ISS 11)
They found that
the intoxicated cohort had a lower incidence of c-spine injuries
and that
c-spine CT had a sensitivity of 94%, a specifity of 99.5% and a negative predicitve value of 99.9%!
In words this means that a negative CT-result for a patient gives us a very high confidence that this negative result is true!
Clearing the c-spine by CT-scan in the intoxicated patient is definitely safe, especially when there are no other injuries or history of a high velocity trauma.
Martin MJ et al. J Trauma Acute Care Surg. 2017 Jul 19
Postoperative pain and delirium is a common concern and currently approached by different interventions. There is some evidence suggesting that ketamine given intra-operatively might have an influence on postoperative pain and delirium. Some anaesthetists commonly give a single dose of ketamine intra-operatively for exactly this reason.
Thumbs up for Ket
Ketamine has kept its fascination in various settings, from retrieval medicine onto the the care of critically ill patients in the ICU. Ketamine reduces postoperative markers of inflammation, is a rapid-acting antidepressant drug with an effect lasting for several days and might have neuroprotective properties.
Ketamine also has become increasingly popular as an adjunct to other sedatives in the ICU. There is evidence showing that ketamine used in the ICU has the potential to reduce cumulative opioid consumption after surgery (Asad E. et al. J Intensive Care Med December 8 2015 ).
Even better: It does not cause any kidney injuries, preserves laryngeal protective reflexes, lower airway resistance and much more...
And: Ketamine is cheap and has been used safely for over 50 years by anaesthetists!
The Dark Side of Ket
But there's the other side of ketamine making all of this a little more complicated. After all, Ketamine is a psychoactive drug and has well known hallucinogenic properties. Developed in the 1960s as a dissociative anaesthetic agent it started to appear on the street in the early 1970s and made its way to the 1980s as Special K, Acid and Super C (Dotson JW et al. J of Drug Abuse, Vol 25, Issue 4, 1995).
From a medical point of view there are some worries that these psychotomimetic effects, which are of concern in the critically ill patient, might predispose to delirium (Erstad BL, J Crit Care, Oct 2016, Vol 35, p 145-149).
The PODCAST Trial
On the background of all this facts this trial revealed some interesting findings. Avidan et al. performed a
Thumbs up for Ket
Ketamine has kept its fascination in various settings, from retrieval medicine onto the the care of critically ill patients in the ICU. Ketamine reduces postoperative markers of inflammation, is a rapid-acting antidepressant drug with an effect lasting for several days and might have neuroprotective properties.
Ketamine also has become increasingly popular as an adjunct to other sedatives in the ICU. There is evidence showing that ketamine used in the ICU has the potential to reduce cumulative opioid consumption after surgery (Asad E. et al. J Intensive Care Med December 8 2015 ).
Even better: It does not cause any kidney injuries, preserves laryngeal protective reflexes, lower airway resistance and much more...
And: Ketamine is cheap and has been used safely for over 50 years by anaesthetists!
The Dark Side of Ket
But there's the other side of ketamine making all of this a little more complicated. After all, Ketamine is a psychoactive drug and has well known hallucinogenic properties. Developed in the 1960s as a dissociative anaesthetic agent it started to appear on the street in the early 1970s and made its way to the 1980s as Special K, Acid and Super C (Dotson JW et al. J of Drug Abuse, Vol 25, Issue 4, 1995).
From a medical point of view there are some worries that these psychotomimetic effects, which are of concern in the critically ill patient, might predispose to delirium (Erstad BL, J Crit Care, Oct 2016, Vol 35, p 145-149).
The PODCAST Trial
On the background of all this facts this trial revealed some interesting findings. Avidan et al. performed a
multicentre, international randomised trial
in which they randomly assigned
672 patients undergoing major cardiac and non-cardiac surgery under general anaethesia
into three groups to either receive a bolus of
placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1·0 mg/kg) after induction of anaesthesia, before surgical incision.
Participants, clinicians, and investigators were blinded to group assignment. They found
NO difference in in the incidence of postoperative delirium among these groups
but
significantly more postoperative hallucinations and nightmares with increasing ketamine doses compared to placebo
in which they randomly assigned
672 patients undergoing major cardiac and non-cardiac surgery under general anaethesia
into three groups to either receive a bolus of
placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1·0 mg/kg) after induction of anaesthesia, before surgical incision.
Participants, clinicians, and investigators were blinded to group assignment. They found
NO difference in in the incidence of postoperative delirium among these groups
but
significantly more postoperative hallucinations and nightmares with increasing ketamine doses compared to placebo
This trial seems well performed with an acceptable sample size. The application of a single dose of ketamine before surgery neither prevented delirium nor induced it. With this sample size it seems safe to say that even if ketamine does prevent delirium, its effect would be rather small.
Furthermore, postoperative pain was not influenced by giving a single dose of ketamine and this is in contrast to previous findings and current guidelines. Importantly, most of the previous studies are smaller than this trial, making these findings remarkable.
But what really drew my attention was the fact that the appearance of hallucinations and night-mares was increased for at least 3 days after surgery.
So if ketamine has no influence on postoperative delirium or pain but does induce hallucinations and nightmares, even 3 days after surgery, current guidelines might have to be revised.
The Bottom Line
- The application of a subanaesthetic dose of ketamine during surgery to tackle postoperative pain and delirium does not seem to be as effective as previously assumed
- The usage of ketamine in this setting even seems to have undesirable side-effects like hallucinations and nightmare - and this effect might even last for up to 3 days!
- This trial provides good reasons to look for other options to prevent postoperative delirium!
(Like dexmedetomidine? The answer to this question has just been answered: READ HERE!)
Furthermore, postoperative pain was not influenced by giving a single dose of ketamine and this is in contrast to previous findings and current guidelines. Importantly, most of the previous studies are smaller than this trial, making these findings remarkable.
But what really drew my attention was the fact that the appearance of hallucinations and night-mares was increased for at least 3 days after surgery.
So if ketamine has no influence on postoperative delirium or pain but does induce hallucinations and nightmares, even 3 days after surgery, current guidelines might have to be revised.
The Bottom Line
- The application of a subanaesthetic dose of ketamine during surgery to tackle postoperative pain and delirium does not seem to be as effective as previously assumed
- The usage of ketamine in this setting even seems to have undesirable side-effects like hallucinations and nightmare - and this effect might even last for up to 3 days!
- This trial provides good reasons to look for other options to prevent postoperative delirium!
(Like dexmedetomidine? The answer to this question has just been answered: READ HERE!)
Sometimes there's this moment you read about medical research in the news... sometimes you read lots of rubbish on medical issues in the news... but sometimes you stop and read, and you don't know what to think. This happened to quite some of us a couple of days ago when reading the headlines in the British Independent:
Well, it's not very often you read the term sepsis in the news but the word 'cure' causes estonishment or rather misbelief. Further reading certainly catches your attention: 'A doctor in the US state of Virginia claims to have found his own cure for sepsis' and 'Since then, he has used it to treat 150 sepsis patients. Just one has died of the condition, claims Dr Marik'. And it's not an article from some remote pseude magazine... no, it has been published in 'Chest'! And all this is not due to some novel molecule... it's all about Vitamin C!
Thanks to #FOAMed quite some smart brains have looked into this topic already...
So here's the most important facts you need to know - in short:
What's the Story?
Paul Marik et al. have published a
single-centre retrospective cohort study
in which they have treated
47 consecutive septic patients over a periode of 7 months with intravenous vitamin C (1.5g 6-hourly), hydrocortisone (50mg 6-hourly) and thiamine (200mg 12-hourly)
and then compared these patients to
47 septic patients treated in their unit during the preceding 7 months
They performed
Propensity score matching
and found
An overall hospital mortality of 40.4% in the control group compared to 8.5% in the intervention group
This means
An absolute risk reduction of 31.9% and also according to the authors none of the patients in the intervention arm died of sepsis!
single-centre retrospective cohort study
in which they have treated
47 consecutive septic patients over a periode of 7 months with intravenous vitamin C (1.5g 6-hourly), hydrocortisone (50mg 6-hourly) and thiamine (200mg 12-hourly)
and then compared these patients to
47 septic patients treated in their unit during the preceding 7 months
They performed
Propensity score matching
and found
An overall hospital mortality of 40.4% in the control group compared to 8.5% in the intervention group
This means
An absolute risk reduction of 31.9% and also according to the authors none of the patients in the intervention arm died of sepsis!
What Does This Mean?
These results are quite amazing on the first look, but there's more behind these numbers. Paul Marik has first of all published an observational study: unblinded, uncontrolled, retrospective and low in patient numbers.
There are several limitations that go hand in hand with studies as such and unblinded before-and-after studies have a lot. A major challenge in conducting observational studies is to draw inferences that are acceptably free from influences by overt biases, as well as to assess the influence of potential hidden biases. One of the biggest drawbacks in this current study is the timely/ seasonal difference when patients have been selected.
If you are interested to have a closer look on this you should read Dan's blog entry on stemlynsblog.org HERE.
Studies like this one are an important part of science, but observational studies are observational... not proof!
There are several limitations that go hand in hand with studies as such and unblinded before-and-after studies have a lot. A major challenge in conducting observational studies is to draw inferences that are acceptably free from influences by overt biases, as well as to assess the influence of potential hidden biases. One of the biggest drawbacks in this current study is the timely/ seasonal difference when patients have been selected.
If you are interested to have a closer look on this you should read Dan's blog entry on stemlynsblog.org HERE.
Studies like this one are an important part of science, but observational studies are observational... not proof!
Why Vitamin C in Sepsis?
There is a scientific rationale behind all of this. As mentioned by Paul in his paper vitamin C levels do fall low in sepsis and the most efficient way to administer it is intravenously. The same is true for thiamin which also goes low in up to one third of all septic patients.
There are two rather small randomised control trials suggesting that vitamin C is safe in septic patients and might actually be of some degree of benefit for the patient.
Vitamin C
- Neutralizes free radicals and has therefore antioxydative properties
- Is an important conenzyme for the procollagen-proline dioxygenase, which itself is necessary for the biosynthesis of stable collagen in our body. Vitamin C deficiency leeds to unstable collagen and therefore scurvy
- Is an important cofactor in the synthesis of steroids like cortisol and catecholamines like dopamine and noradrenalin as well
- and it has many more functions that go beyond the scope of this blog entry!
However, the importance of vitamin C in the treatment and prevention of diseases like e.g. the common cold or influenza remains highly contrversial. The observation of some moderate positive influence on the course of disease in some studies could not be reproduced in other trials.
Under normal circumstances vitamin C deficiency is practically non-existent in Europe, but becomes a fact during sepsis. If this is clinically relevant in septic patients seems plausible but remains to be elucidated.
Shailja Chambial, Shailendra Dwivedi, Kamla Kant Shukla, Placheril J. John, and Praveen Sharma. Vitamin C in Disease Prevention and Cure: An Overview. Indian Journal of Clinical Biochemistry. Oktober 2013; 28(4): S. 314–328
H. Hemilä, E. Chalker: Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews. 2013
R. M. Douglas, E. B. Chalker, B. Treacy: Vitamin C for preventing and treating the common cold. In: Cochrane Database of Systematic Reviews. 2000; 2:CD000980.
Another great read into the details: Josh Farkas from pulmcrit
There are two rather small randomised control trials suggesting that vitamin C is safe in septic patients and might actually be of some degree of benefit for the patient.
Vitamin C
- Neutralizes free radicals and has therefore antioxydative properties
- Is an important conenzyme for the procollagen-proline dioxygenase, which itself is necessary for the biosynthesis of stable collagen in our body. Vitamin C deficiency leeds to unstable collagen and therefore scurvy
- Is an important cofactor in the synthesis of steroids like cortisol and catecholamines like dopamine and noradrenalin as well
- and it has many more functions that go beyond the scope of this blog entry!
However, the importance of vitamin C in the treatment and prevention of diseases like e.g. the common cold or influenza remains highly contrversial. The observation of some moderate positive influence on the course of disease in some studies could not be reproduced in other trials.
Under normal circumstances vitamin C deficiency is practically non-existent in Europe, but becomes a fact during sepsis. If this is clinically relevant in septic patients seems plausible but remains to be elucidated.
Shailja Chambial, Shailendra Dwivedi, Kamla Kant Shukla, Placheril J. John, and Praveen Sharma. Vitamin C in Disease Prevention and Cure: An Overview. Indian Journal of Clinical Biochemistry. Oktober 2013; 28(4): S. 314–328
H. Hemilä, E. Chalker: Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews. 2013
R. M. Douglas, E. B. Chalker, B. Treacy: Vitamin C for preventing and treating the common cold. In: Cochrane Database of Systematic Reviews. 2000; 2:CD000980.
Another great read into the details: Josh Farkas from pulmcrit
More Ifs and Buts
Sepsis is not a disease, its a clinical syndrome that has physiologic, biologic and biochemical abnormalities caused by a dysregulated inflammatory response to infection. The fact that different definitions have evolved since the early 1990s shows that we still struggle to definde sepsis as a single entity. This is one reason why a single therapy might not always be the best for each diesease causing sepsis.
Paul Marik’s publication is interesting and deserves respect. It’s an observational study but provides no evidence by far. Vitamin C might be an interesting novel approach to sepsis but the term ‘cure’ used in the media is inappropriate and misleading.
The term ‘cure for sepsis’ also implicates that vitamin C is a cure for all infections causing sepsis and is therefore problematic.
Paul Marik’s publication is interesting and deserves respect. It’s an observational study but provides no evidence by far. Vitamin C might be an interesting novel approach to sepsis but the term ‘cure’ used in the media is inappropriate and misleading.
The term ‘cure for sepsis’ also implicates that vitamin C is a cure for all infections causing sepsis and is therefore problematic.
The Current Bottom Line
- The study published by Marik et al. is purely observational and provides no proof at all.
- Just because vitamine C might be safe in Sepsis does not mean this has to be given. At this stage no recommendation can be made for the use of vitamin C in sepsis.
- Studies like these are an part of research itself - However, the use of the term 'cure' seem problematic and inappropriate in this context.
Marik et. al, J Chest 2017
What's the Problem?
Most radiologic exams, especially computed tomography (CT) scans, use iodinated contrast media in order to improve image quality and therefore diagnostic accuracy. The decision on whether to use IV contrast media is also made on the background of pre-existing renal function as the use of these agents has been linked to increased risk of adverse events like: acute kidney injury, initiation of dialysis, renal failure, stroke, myocardial infarction, and death.
-> So called 'contrast-induced nephropathy' or short CIN!
The REAL PROBLEM is that randomising patients to receive or not receive a contrast-enhanced imaging study when indicated is simply not feasible.
- It has been presumed that these agents are a direct cause of acute kidney injury - and therefore dangerous ☠
But, Hold On: Is There Really a Problem?
The causal relationship between the application of IV contrast media and the development of acute kidney injury has recently been questioned - Seriously questioned!
- It is interesting to notice that most of our current understanding of contrast-induced nephropathy derives from arterial angiography studies.
- Also, many studies looking into this problem were performed without any control populations. These investigators obviously assumed that CIN undoubtably exists but did not compare their cohort to patients not receiving contrast media!
Mitchell AM et al. nn Emerg Med. 2015 Sep;66(3):267-274 or Mitchell AM et al. lin J Am Soc Nephrol. 2010 Jan;5(1):4-9. doi: 10 and more!
🤔
- As a matter of fact, serum creatinine level fluctuations (meeting the criteria for contrast induced nephropathy) occur in patients in patients undergoing unenhanced CT at similar rates to those published after contrast-enhanced CT. Newhouse JH et al. (see reference below) for instance looked at a total of over 32'000 patients and noticed that creatinine level increases in patients who are not receiving contrast material as often as it does in published series of patients who are receiving contrast material.
AJR Am J Roentgenol. 2008 Aug;191(2):376-82
Newhouse already suspected that CIN may have been overestimated so far! Also other studies found no increased of acute kidney injury after after contrast media administration in any patient group, regardless of baseline renal function.
Crit Cloud review from March 2014
Crit Cloud review from January 2015
Maybe There is No Major Problem
Two recently published paper further challenge the paradigm of contrast-induced nephropathy.
Hinson J et al. published a single-center retrospective cohort study in 2016 in which a total of 17'934 patient visits to their emergency department over a period of 5 years were included. They analysed three patient groups that where demographically similar: contrast-enhanced CT, unenhanced CT and no CT scan performed. In this largest controlled study of it's kind no difference was found in the incidence of acute kidney injury.
Hinson J et al. Annals of Emergency Medicine, 2017; DOI: 10.1016/j.annemergmed.2016.11.021
And just now Wilhelm-Leen et al. have published their analysis of almost 6'000'000 hospitalised patients in the united states and their risk of radio-contrast associated nephropathy. Their results strongly suggest, that the incremental risk of AKI that can be attributed to contrast-media is modest at worst, and almost certainly overestimated!
Wilhelm-Leen Emilee, J Am Soc Nephrol 28: 653-659,2017
A most recent editorial by Lopez-Ruiz at al. puts this new knowledge into a new perspective.
J Am Soc Nephrol. 2017 Feb;28(2):397-399
- If contrast induced nephropathy does exist, it's relevance in clinical practice seems to have been overestimated so far!
Is There a Way to Prevents Contrast-Induced Nephropathy?
The application of sodium bicarbonate, N-acetylcysteine, statins, ascorbic acid and pre-hydration with IV fluids have been recommended for the prevention of CIN in patients with compromised renal function. Among all of these measures hydration with intravenous saline is considered the cornerstone in the prevention of CIN.
And luckily enough just now The Lancet provides us with a first answer to this specific question. The AMAZING trial published in February 2017 provides fairly good evidence that prophylactic hydration with normal saline does not lower the incidence of CIN.
EC Nijssen et al. The Lancet, Feb. 2017
The Bottom Line:
- Until proven otherwise IV contrast media should be considered potentially nephrotoxic. This is supported by preclinical and cardiac studies. If this is relevant in clinical practice (escpecially for CT scans) is not proven so far... but also difficult to disapprove!
- The risk of contrast-induced nephropathy certainly has been oversetimated so far!
- While prophylactic hydration of the patient has no benefit in regards of CIN, keeping patients well hydrated in general is certainly strongly recommended.
- Quick and proper treatment of the patients underlying condition is most probably more important than worrying about CIN and therefore withholding an indicated enhanced CT-scan!
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