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
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
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!)
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
Ketamine's success seems unstoppable:
+++ Anaesthesiologists are opening private clinics for off-label infusions of ketamine for depression http://bit.ly/1IGYTcI +++ Dr. Jim Roberts says #ketamine is an ideal treatment for excited #delirium: http://emn.online/Dec15InFocus +++ Major #ketamine treatment trial to start in 2016 http://m.huffpost.com/au/entry/8501942 +++ More impressed every day with low dose ketamine for pain management! https://www.youtube.com/watch?v=DgckjVVBb48 ...
Intravenous ketamine is also used in critical care units and to my knowledge most clinicians use ketamine as an adjunct to other sedatives. This might be for patients on mechanical ventilation, intubation procedures or simply as an additive to a patient-controlled analgesia pump. I personally think ketamine is one of the essentials in ICU's, but what does the evidence say.
Asad et al. have performed a systematic review on the usage of ketamine as a continuous infusion (>24h) in intensive care patients. The aim was to find evidence in favour for the utilisation of ketamine in the ICU.
As a result of this review - current evidence suggests that:
- In critically ill postoperative patients ketamine has the potential to reduce the cumulative morphine consumption at 48h compared to morphine only
- Several trials show the potential safety of ketamine in regards of cerebral haemodynamics in patients with traumatic brain injury, improved gastrointestinal motility and decreased vasopressor requirements
- One observational study and case reports suggest that ketamine is safe, effective and may have a role in patients who are refractory to other therapies
Our conclusion: THUMBS UP for ketamine in the ICU
Asad E. et al. J Intensive Care Med December 8, 2015
A good question, but do you actually know. Most ICU's have their standard modes of ventilation and we are busy enough concentrating on the wright PEEP, the perfect tidal volume or prone positioning the patient. But does the mode of ventilation actually have an impact on the outcome? Chacko et al. had a look at exactly this question and performed a systematic review on this topic:
- Early mortality: There is only some moderate-quality evidence suggesting that pressure controlled ventilation might be of benefit, although this was not observed in the long term follow-up!
- Duration of mechanical ventilation: no apparent difference between pressure- and volume-controlled ventilation
- ICU length of stay: no apparent difference between pressure- and volume-controlled ventilation
- incidence of barotrauma: no apparent difference between pressure- and volume-controlled ventilation
- Extrapulmonary organ failure: One underpowered study in favour of pressure controlled ventilation
- Infective complications, Quality of life: To this date no studies available
Conclusion: Current evidence shows no difference between pressure controlled and volume controlled ventilation in ARDS.
Cochrane, Clinical Answers OPEN ACCESS
Chacko B, Peter JV, Tharyan P, John G, Jeyaseelan L. Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No.: CD008807. OPEN ACCESS
When performing a kidney transplantation nowadays up to 50% of recipients developed a delayed graft function which is defined as the need of dialysis within seven days. The authors of this recently published NEJM-article asked themselves whether mild hypothermia might influence outcome in this regard.
In order to answer this question the investigators assigned organ donors after declaration of death according to neurologic criteria into two groups. They were either treated with mild hypothermia (34 to 35°C) or with normothermia (36.5 to 37.5°C). The target temperature was maintained until the patients were transferred to theatre for transplantation.
Primary outcome of this trial was delayed graft function among recipients. Secondary outcomes included the rates of individual organs transplanted into each treatment group at the total number of organs transplanted from each donor.
This trial had to be stopped early as an interim analysis showed significant efficacy of mild hypothermia. Up to this point a total of 572 patients received a kidney transplant (285 in the hypothermia group and 287 in the normothermia group). 28% of recipients in the hypothemia group developed delayed graft function compared to 39% in the normothermia group.
The authors therefore conclude that mild hypothermia significantly reduces the rate of delayed graft functions among recipients.
Anyhow, it seems reasonable not to get rid of your cooling devices!
Read more about the controversies of hypothermia in the ICU:
The Targeted Temperature Management Trial: Nielsen N, et al. New Engl J Med. 2013 Dec;369(23):2197-206
The 2 trials that introduced therapeutic hypothermia into ICU practice:
The Hypothermia After Cardiac Arrest Study Group, Holzer at al. New Engl J Med. 2002 Feb;346(8):549-556
Bernard S.A. et al. New Engl J Med. 2002 Feb;346(8):557-563
Review article on therapeutic hypothermia for non-VF/VT cardiac arrest:
Sandroni S. et al. Crit Care Med; 2013;17:215
Pyrexia and neurological outcome:
Leary M. et al. Resuscitation. 2013 Aug;84(8):1056-61
BIJC post on: The Effect of Pre-Hospital Cooling: Rather Worrying Results
Beverley Hunt at al. have just published an excellent practical guideline for the haematological management of major haemorrhage which also serves a a great educational review on this topic... an excellent piece of work!
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?
A number of things we do for patients in the ICU we simply do... because it has been always done. Maybe because it seems to make sense or because we were simply taught to do so. One of these treatments is the application of oxygen to patients suffering of myocardial infarction. But in fact the impact of this measure is not that well established and we know that high concentrations of oxygen can actually be harmful. Some previous studies suggest possible increase in myocardial injury.
Stub et al. therefore performed a multicenter, prospective, randomised controlled trial comparing oxygen (8 L/min) with no supplemental oxygen in patients with STEMI diagnosed on paramedic 12-lead electrocardiogram. They finally included 441 patients into their study.
Their primary endpoint was evaluation of infarction size assessed by the cardiac enzymes troponin (cTnI) and creatine kinase (CK). While troponin levels did not differ there was a significant difference in the mean peak CK levels, being higher in the group with oxygen applied. By looking at the secondary endpoints they also found an increase in the rate of recurrent myocardial infarctions and in the frequency of cardiac arrhythmia among the oxygen group. Finally at 6-months the oxygen group had an increase in myocardial infarct size on cardiac MRI.
They conclude that patients with myocardial infarction but without hypoxemia may actually not benefit of supplemental oxygen therapy.
Time to question our automatisms when treating patients.
Stub et al. Circulation. 2015 Jun 16;131(24):2143-50.
In the late 1960's the technology of counter-pulsation by using an intra-aortic balloon pump (IABP) was introduced into clinical work. Based on the principle of diastolic inflation and systolic deflation, IABP counter-pulsation improves diastolic coronary artery blood flow and decreases left ventricular afterload. Up to the year 2009, 2012 respectively, the usage of an IABP in patients with ST-segment elevation myocardial infarction and cardiogenic shock was considered a class IC recommendation (reminder: levels of evidence).
Since then a couple of well conducted, larger trials have failed to show a positive impact of IABP especially on mortality. In regards of the most recent meta-analysis in JAMA we provide a short overview of the most important publications. It's interesting to see that the balloons undermining started with a meta-analysis and for the the time being ends with one.
The first notable hole in the ballon was caused by Sjauw et al.'s systematic review and meta-analysis in the European Heart Journal in 2009. Their pooled randomized data consisting of two separate meta-analyses did not support the use of an IABP in patients with high risk STEMI. They concluded that there is insufficient evidence endorsing the current guideline recommendation for the use of IABP therapy in the setting of STEMI complicated by cardiogenic shock.
This publication was one of the main reasons for the expert panel of the European Society of Cardiology to change the recommendation (ESC Guidelines 2012) to use an IABP in patients with STEMI from IC to IIB.
Stitch 2 and 3
In the same year 2012 Thiele et al. published their first IABP-SHOCK II results in the NEJM. Their
randomized, prospective, open-label, multicenter trial showed no reduction in the 30-day mortality compared to the best available medical therapy alone in patients with myocardial infarction-induced cardiogenic shock and planned early revascularization (PCI or CABG).
One year later the IABP-SHOCK II investigators published their final 12-months results in The Lancet. They came to the final conclusion that in patients undergoing early revascularization for myocardial infarction with cardiogenic shock, IABP did not reduce 12-month all-cause mortality.
Stitch no. 4
In 2013 Ranucci at al. presented the results of their single-center prospective randomized controlled trial looking at the usage of a preoperative IABP in high-risk patients undergoing surgical coronary revascularization. By looking at a total of 110 patients with an ejection fraction below 35% and no hemodynamic instability there was no improvement in outcome when inserting an IABP preoperatively.
Preliminary Final Stitch
So finally Ahmad and his team decided to assess IABP efficacy in acute myocardial infarction by performing an updated meta-analysis. Main outcome was 30-day mortality. They included 12 eligible RCTs randomizing 2123 patients and found no improvement in mortality among patients with acute myocardial infarction... regardless of whether patients had cardiogenic shock or not!
A look at another 15 eligible observational studies with a total of 15 530 patients showed basically conflicting results which was explained by the differences between studies in the balance of risk factors between IABP and non-IABP groups.
It seems that the IABP fails to show its assumed efficacy in patients with myocardial infarction and cardiogenic shock, especially when early revascularization (PCI or CABG) is available.
As a general consideration and also when no early revascularisation is available the use of another left-ventricular assist device like the Impella pump might prove to be a good and easy to use alternative (see blow).
Sjauw KD et al. Eur Heart J 30: 459-468
ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 33: 2569-2619 OPEN ACCESS
Thiele et al. N Engl J Med 2012; 367:1287-1296 OPEN ACCESS
Thiele et al. The Lancet, Volume 382, Issue 9905, Pages 1638 – 1645
Crit Care Med. 2013 Nov;41(11):2476-83
JAMA Intern Med. Published online March 30, 2015
Short film on the principle of the Impella pump 2.5. Bare in mind that this device can actually be easily inserted in the environment of ICU and positioned by using transthoracic echo TTE.
Microbiologically confirmed ventilator-associated pneumonia (VAP) or ventilator-associated conditions (VAC, e.g. worsening oxygenation) in intubated patients remains a major concern in ICU's. VAP is defined as a hospital-acquired pneumonia which develops within 48-72 hours after endotracheal intubation.
To prevent this complication ICU's uniformly have adapted the VAP-bundle, a bunch of measures aiming to prevent ventilator-associated pneumonia. Unfortunately the evidence of the VAP-bundle is not as robust as one might think it is. Here's the evidence of some elements of the VAP bundle:
- Elevation of the head to bed 45° (low evidence)
- Daily sedation interruptions (the impact on reducing VAP has not been shown so far)
- Daily oral chlorhexidine rinses (low evidence)
... it's most likely the combination of measures that is of benefit to the patient... hopefully! But hold on, there is another intervention that finally brings quite some evidence with it!
Active suctioning of the subglottic area, where nasal-oral secretions gather and create a rich culture medium for all sorts of micro-organisms, also aims to reduce the incidence of VAP. In contrast to the classical VAP-bundle the evidence here is strongly in favour for these devices!
In 2005 four registrars in cardiothoracic surgery looked into this topic and summarised their efforts online on Best Evidence Topics, best bets.org. In this blog they review 13 relevant articles on the use of subglottic suctioning and conclude: subglottic suction significantly reduces the incidence of VAP in high risk patients - which means a NNT of 8 if ventilated for more than 3 days. They also mention that this measure is cost effective, despite the more expensive tubes.
In the same year Dezfulian et al. presented a systematic meta-analysis of randomized trials in the American Journal of Medicine. They ended up with 5 studies including 869 patients. They also came to the conclusion that subglottic secretion drainage is effective in preventing VAP in patients expected to be ventilated for more than 72 hours.
In 2011 Hallais et al. looked into the issue of cost-effectiveness with a cost-benefit analysis. Even when assuming the most pessimistic scenario of VAP incidence and costs the replacement of conventional ventilation with continuous subglottic suctioning would still be cost-effective.
In 2011 Muscedere et al. published an 'official' review article in Critical Care Medicine and also ended up with 13 randomised clinical trial, most of them the same 'BestBETs' had already identified 6 years before. It is therefore not surprising to see that they also found a highly significant reduction in VAP. They were also able to demonstrate a reduction in ICU length of stay and duration of mechanical ventilation, although the strength of this association was weakened by heterogeneity of study results.
We finally would like to mention the latest randomised controlled trial on this topic which was published in Critical Care Medicine this January 2015. Damas et al. randomly assigned 352 patients to either receive subglottic suctioning or not. Again sublottic suctioning significantly reduced VAP prevalence and therefore also antibiotic use.
At least we have identified one area in critical care where an impressive pile of evidence supporting the use of subglottic suctioning in long-term intubated patients is present... and even better: cost-effective analyses also come out in great favour for this measure!
Take-home message: Subglottic suctioning does prevent VAP in patients likely to be ventilated more than (48-) 72 hours and should be used in these situations.
Review BestBETs 2005
Dezfulian C et al. Am J Med. 2005 Jan;118(1):11-8
Hallais C. et al. Infect Control Hosp Epidemiol. 2011 Feb;32(2):131-5
Muscedere J et al. Crit Care Med. 2011 Vol. 39, No. 8
Damas P et al. Crit Care Med. 2015 Jan;43(1):22-30
Little Christmas Present: Open Access 'Anaesthesia' Supplement on Transfusion, Thrombosis and Bleeding Management
'Anaesthesia', the Journal of the Association of Anaesthetists of Great Britain and Ireland have published an Open Access Supplement on various aspects of Transfusion, Thrombosis and Bleeding Management. This is an excellent opportunity to update your knowledge in this field and actually compulsory for anyone involved actively in critical care.
The supplement consists of multiple review articles which are kept nice and short and are perfect for reading in between...
In Conclusion: Reading highly recommended!
On following website you can find a list of all articles including links to the full text:
Anaesthesia, Vol. 70, Issue Supplement s1, January 2015: Transfusion, Thrombosis and Bleeding Management