As posted on BIJC before, Asad et al. had performed a systematic review on the usage of ketamine as a continuous infusion (>24h) in intensive care patients. The same authors have now published a narrative review providing a more depth discussion about the pharmacological and pharmacokinetic properties of ketamine. Also they present recommendations for dosing and monitoring in an ICU setting.
The Goodies of Ket
Current evidence shows that Ketamine...
- Has no adverse effects on the gastrointestinal tract (bleeding) and does not cause acute kidney injury (compared to nonsteroidal anti-inflammatory drungs, NSAID's)
- Does not negatively influence bowel motility (in contrast to opioids)
- Preserves laryngeal protective reflexes
- Lowers airway resistance
- Increases lung compliance
- Is less likely to cause respiratory depression
- Is sympathomimetic, facilitates adrenergic transmission and inhibits synaptic catecholamine reuptake, therefore increasing heart rate and blood pressure
The Concerns of Ket
- Might increase pulmonary airway pressure and therefore aggravate pulmonary hypertension
- Might cause well known psychotomimetic effects which are of concern in the critically ill patient as this might predispose to delirium
- Interacts with benzodiazepines via the P450 pathway which could result in drug accumulation and prolonged recovery
Concerns Proven Wrong
- Ketamine need not to be avoided in patients at risk for seizures, particularly when used for analgosedation for short periods in the ICU setting
- Current evidence shows no increased intracranial pressure or associated adverse neurologic outcomes associated with ketamine administration in critically ill patients
The use of ketamine for analgosedation in the ICU continues to lack high-level evidence.However, it is effectively used around the globe and remains an attractive alternative agent for appropriately selected patients. Taking current knowledge and evidence into account this is especially true for patients with severe pain unresponsive to conventional therapies.
Taking precautions and contraindications into account ketamine is considerably safe and even avoids potentially adverse side effects of other agents used.
Erstad BL, J Crit Care, Oct 2016, Vol 35, p 145-149
Fluids are one of the cornerstones in the treatment of patients with shock. But with any drug applied, also fluids can harm if given inappropriately! While inadequate fluid resuscitation might result in tissue hypoperfusion and worsening of end-organ function, to much fluid might lead to problems like pulmonary oedema and finally increased mortality. Many measures are used in clinical practice, but most of them lack specificity and are not very representative as a sole marker. One of the better methods to evaluate fluid requirements is the use of dynamic measures that estimate the change in cardiac output (CO) in response to a fluid bolus.
In this regard the use of point-of-care ultrasound (POCUS) has become increasingly attractive in order to use basic critical care ultrasound to asses the need of fluids in a specific clinical setting. Lee at al. have now looked at the sonographic assessment of the inferior vena cava and lung ultrasound in order to quite fluid therapy in intensive care. By taking into account current evidence they have produced an algorithm using these measures to help guiding fluid therapy.
As with any measurement in critically ill patients the pathophysiologic cause of shock must be taken into account. The algorithm presented here seems to work best in patients in hypovolemic shock. To fully understand the following algorithm and its limitations we recommend to read the open access article (see link below).
The algorithm provided is a helpful tool to help assess the need of fluids in a simple and quick manner.
Lee C et al. J of Crit Care 31 (2016) 96-100 OPEN ACCESS
Sepsis certainly keeps us going... either when treating patients on ICU or when it comes to the discussion on what actually sepsis is and how to define it. So far the SIRS (Systemic Inflammatory Response Syndrome) criteria have provided some degree of handle to cope with this syndrome but of course we weren't all quite happy with this. In fact every person with any sort of infectious disease will respond with 2 or more SIRS criteria... but doesn't necessarily have to be septic. As a matter of fact a SIRS is nothing else but a physiologic response to any sort of inflammation.
The New Approach to Sepsis - The SOFA
The new international consensus definitions for sepsis and septic shock try to focus on the fact that sepsis itself defines a life-threatening organ dysfunction caused by a dysregulated host response to infection. By saying this the aim is to provide a definition that allows early detection of septic patients and allow prompt and appropriate response. As even a modest degree of organ dysfunction is associated with an increased in-hospital mortality the SOFA score (Sequential or 'Sepsis-related' Organ Failure Assessment) was found to be the best scoring system for this purpose. It's well known, simple to use and has a well-validated relationship to mortality risk.
Sepsis (related organ dysfunction) is now defined by a SOFA score increase of 2 points or more
The Quick Approach to Sepsis - The BAT
In the out-of-hospital setting, on the general wards or in the emergency department the task force recommends an altered bed side clinical score called the quickSOFA - or alternatively 'the BAT' score:
The New Approach to Septic Shock -Vasopressors and Lactate
Septic shock is now defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of death than sepsis alone. Keeping a long story short:
Septic Shock is now:
- The need for vasopressors to maintain a mean arterial pressure of at least 65mmHg
- a serum lactate level of more than 2mmol/L... after adequate fluid resuscitation
The Bottom Line:
The way it looks like we are left with Sepsis and Septic Shock
Severe Sepsis has vanished and the question remains, whether these new definitions will actually benefit the ones that need it most... our septic patients!
Singer M et al. JAMA. 2016;315(8):801-810.
Seymour CW et al. JAMA. 2016;315(8):762-774.
Shankar-Hari M et al. JAMA. 2016;315(8):775-787.
November 2015, the Difficult Airway Society have published their updated guidelines for management of difficult intubation in adults. Again DAS provide an excellent overview on unanticipated difficult intubations in adults... worth reading for anyone involved in critical care!
When reading this article I couldn't help myself putting a special focus on the controversial issue of cricoid pressure (CP) for rapid sequence induction (RSI). This topic has become a major matter of debate as scientific evidence of its effect on preventing aspiration of gastric content is basically lacking. There is quite some evidence available showing that cricoid pressure might actually impair intubation or potentially harm the patient. More background information and links on this topic you can find here. While some guidelines have actually 'softened' or abandoned the recommendation for the use of CP, most of them have not... and continue to recommend CP. It was therefore of great interest to see what the panel of the DAS would come up with!
For anaesthetists working in Britain and Ireland the DAS guidelines are of special interest as they represent some sort of legal binding on how to proceed at their daily work. We took a closer look at the new guidelines... and got surprised:
"This (CP) is a standard component of rapid sequence induction in the UK". Ok... so no change there! This statement is pretty clear and leaves no space for interpretation - sounds imperative. A little less clear are the following text passages on why CP remains a standard component.
"It is often overlooked that cricoid pressure has been shown to prevent gastric distension during mask ventilation and was originally described for this purpose"... Well, actually cricoid pressure was originally described by Brian Arthur Sellick in the Lancet in 1961 as a preliminary report of an un-controlled case study and the purpose of cricoid pressure was to control regurgitation of gastric content during induction of anaesthesia.
CP and Gastric Insufflation
The reference cited in the context of gastric insufflation and cricoid pressure is an article by Salem and Sellik form Anaesthesia and Analgesia in 1974 (read the original article here). They write: one aim of CP is the prevention of aspiration. The other one is the prevention of gastric insufflation during mask ventilation. The presented evidence in that regard though is not really convincing:
a) A historical letter of Dr. William Cullen... dated back in 1774!
b) The other reference is an article by Salem himself on the 'efficacy of cricoid pressure in preventing gastric inflation during bag-mask ventilation in paediatric patients, but not adults!
Another article cited by the DAS (Obstetric Anaesthetists' Association/Difficult Airway Society difficult and failed tracheal intubation guidelines – the way forward for the obstetric airway Br. J. Anaesth. (2015) 115 (6): 815-818) actually recommends gentle ventilation with low insufflation pressure during RSI which should not overcome correctly applied cricoid pressure. This suggests that CP makes gentle bag-mask ventilation safe.
Indeed, Lawes et al. already showed in 1987 that when bag-mask ventilating, it was not possible to cause gas to enter the stomach in any patient with a patent airway when cricoid pressure was applied. BUT he also stated that: In the absence of cricoid pressure the lungs of all the patients could be ventilated “gently” satisfactorily by hand without gas entering the stomach.
The Bottom Line
Going through these overall brilliant guidelines by the DAS I still haven't been convinced about the usefulness of cricoid pressure and resume (once again):
- Cricoid pressure for rapid sequence induction remains a non-evidence-based manoeuvre and should be seriously questioned!
And by the way, I feel the DAS actually knows that. You have to acknowledge what Hagberg writes in the BJA editorial:
..."the application of CP during rapid sequence induction remains a matter of debate; some believe in its effectiveness in preventing pulmonary aspiration, whereas others believe it should be abandoned because of the paucity of scientific evidence of benefit and possible complications."
..."The literature does demonstrate that the use of CP is likely to make airway interventions, such as mask ventilation, SGA insertion, direct laryngoscopy, and intubation more difficult."
..."As a result of the lack of sufficient scientific evidence that CP reduces regurgitation, in addition to evidence that it may interfere with airway management..."
Difficult Airway Society DAS 2015 guidelines for management of unanticipated difficult intubation in adults, Br. J. Anaesth. 2015 OPEN ACCESS
BIJC post on Cricoid Pressure 04/2014
Hagberg et al. DAS 2015 Guidelines - Editorial, Br. J. Anaesth. 2015, 1-3 OPEN ACCESS
Lawes et al. Inflation Pressure, Gastric Insufflation and Rapid Sequence Induction, Br. J. Anaesth. 1987
Since the year 2000 the International Liaison Committee on Resuscitation (ILCOR) continues to evaluate all evidence and updates their recommendations in 5-year cycles. The most recent ILCOR 2015 International Consensus Conference was held in Dallas last February and the new treatment recommendation are out now.
Resuscitation remains one of the most challenging situations in health care. Providing basic and advanced cardiac life support gives you the opportunity to virtually safe a patients life but in a very limited period of time. It is an enormous challenge to consider all emerging evidence and pack this into simple and useful guidelines.
It is imperative to for any health care provider to get familiar with the updated guidelines and major changes. Below you can find all relevant links to get the reading going.
The team of BoringEM.org in Canada have provided some excellent infographics to visualise all important changes in the new treatment guidelines since 2010. You should also note that the Canadian Heart & Stroke Association and the American Heart Association have just published the 'HIGHLIGHTS of the 2015 American Heart Association Guidelines Update for CPR and ECC', an excellent summary of the new recommendations and changes. So if you can't find the time to read all of the publication in 'Circulation', this will certainly provide all information you need to know.
Summary of the Canadian Heart & Stroke Association and the American Heart Association: HIGHLIGHTS of the 2015 American Heart Association Guidelines Update for CPR and ECC
The original publication in Circulation, October 20, 2015, Volume 132, Issue 16 suppl 1
The Most Important Changes (Click to Enlarge)
The Updated Algorithms (Click to Enlarge)
|Acute Exacerbations in Patients with IPF,Kim Respiratory Research 2013, 14:86|
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The authors look at this topic point for point and review current literature in an easy to understand sort of manor. They define major blood loss when it leads to a heart rte of >110/Min or a systolic blood pressure of less than 90mmHg, or simply said: when bleeding becomes haemodynamic relevant. In general it is recommended to have a major haemorrhage protocol at hand (1D) and all staff should be trained to recognise major blood loss early (1D).
Here's a summary of the recommendations made by the British Committee for Standards in Haematology (BCSH):
In Major Haemorrhage....
Red Blood Cells RBC
- Hospitals must be prepared to provide emergency Group 0 red cells and group specific red cells (1C)
- Patients must have correctly labelled samples taken before administration of emergency Group 0 blood (1C)
- There is NO indication to request 'fresh' or 'young' red cells (under 7d of storage, 2B)
- Note: The optimum target haemoglobin concentration (Hb) in this clinical setting in general is NOT established. Current literature shows a tendency towards restriction towards 70-90g/L, but the BCSH makes no recommendations therefore (see blow)
Cell Salvage (e.g. cell saver)
- 24h access to cell salvage should be available in cardiac, obstetric, trauma and vascular centres (2b)
- Use haemostatic tests regularly during haemorrhage, every 30-60min, depending on severity of blood loss (1C)
- Measure platelet count, PT, aPTT (1C)
- Note: The BCSG does not recommend TEG and ROTEM at this stage
Fresh Frozen Plasma FFP
- Use FFP in a 1:2 ratio with RBC initially (2C)
- Once bleeding is under control administer FFP when PT and/or aPTT is >1.5 times normal (recommended dose 15-20ml/kg, 2C)
- The use of FFP should not delay fibrinogen supplementation if necessary (2C)
- Supplement fibrinogen when levels fall below 1.5g/L
Prothrombin Complex Concentrates PCC
- Do not use PCC
- Keep the platelet count >50 x 10^9/L (1B)
- If bleeding persists give platelets if count falls below 100 x 10^9/L (2C)
Tranexamic Acid TA
- Give tranexamic acid as soon as possible to patients with, or at risk of major haemorrhage (Recommended dose: 1g IV over 10min, followed by 1g IV over 8h, 1A)
- Note: TA has no known adverse effects
- Note: Aprotinin is not recommended
Recombinant Activated Factor VIIa (Novo Seven)
- Do not use
Specific Clinical Situations
- Fibrinogen levels increase during pregnancy to 4-6g/L
- In major obstetric haemorrhage fibrinogen should be given when levels are <2.0g/L (1B)
- Use restrictive strategy for RBC transfusion is recommended in most patients (1A)
- Transfuse adult trauma patients empirically with a 1:1 ratio of FFP : RBC (1B)
- Consider early use of platelets (1B)
- Give tranexamic acid as soon as possible (Dose 1g over 10min and then 1g over 8h, 1A)
Prevention of Bleeding in High-Risk Surgery
- Use tranexamic acid (Dose 1g over 10min and then 1g over 8h, 1B)
Hunt B et al. British J Haemat, July 6 2015
Read more HERE:
Great Review on Transfusion, Thrombosis and Bleeding Management
Restricitve Transfusion Threshold in Sepsis, the TRISS Trial
Transfusion: Harmful for Patients Undergoing PCI?
These guidelines outline the nature and properties of biofilms and and their implications on mostly chronic infections caused. As biofilms are very common in critically ill patients it is important to know what specific problems you might encounter, how to proceed and perform a proper diagnosis and what are the essential bits and pieces in the prevention and treatment of biofilm infections.
The article is OPEN ACCESS: Clin Microbiol Infect. 2015 Jan 14. pii: S1198-743X(14)00090-1.
ARISE and ProCESS had been published before (read here) and both of them showed no difference between EGDT and 'usual care'.
ProMISe included 1251 patients with severe sepsis or septic shock that were admitted to a total 56 hospitals in the UK. Again classical EGDT with measurement of continuous central venous oxygenation was compared to so called 'usual treatment'. It's remarkable to notice that in the 'usual treatment' group about half of the patient didn't get a central line and central venous oxygenation wasn't even measured in the ones who got one. And here's the result:
There was no difference in 90-day mortality and no differences in secondary outcomes. In contrast EGDT actually increased costs.
It has become difficult to ignore these three trials!
Our conclusion: The classical EGDT therapy has ended here and now... but EGDT will keep its central role in the treatment of septic patients!
- Identify septic patient quickly, start screening for patients if indicated
- Administer antibiotics within the first our of recognition of sepsis
- Start IV-fluid therapy immediately
- Take (blood) cultures as quick as possible, but do not delay antibiotic treatment
- Aim for a reasonable mean arterial pressure (e.g. 65mmHg)
- Aim for a sufficient urinary output (0.5ml/h)
- Central venous pressure (CVP) certainly and most probably central venous oxygenation (ScvO2) are not parameters to measure fluid responsiveness
- Lactate remains an issue of debate
- Simple: Whatever the physician feels is best!
ProMISe Trial, Mouncey et al. N Engl J Med. 2015 Mar 17.
BIJC Review on ARISE and ProCESS
Picture displayed taken from the Ice Cream Trilogy by Wright, Pegg and Frost
As these guidelines are open access it can be considered mandatory Free Open Access Meducation FOAMed. Below is a summary of the Recommendations according to specific patient groups.
It's interesting to notice that digoxin still plays a role in patients with heart failure, especially when looking at the findings of Turakhia et al. in JACC, Aug 19 2014.
J Am Coll Cardiol. 2014;64(21):2246-2280 OPEN ACCESS
BIJC post on dixogin in critical care
For A Smile ; )