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
Dexmedetomidine has shaken up the usual sedatives in ICU but remains a matter of debate among intensivists. One question is whether the higher costs compared to midazolam are justified by clinical advantages. There is research available suggesting that dexmedetomidine might be an attractive alternative to standard sedatives especially in regards of time to extubation and costs (Turinen et al., Jacob et al.). This seems to hold true for moderate to light sedation of intubated patients.
I've stepped over this prospective, double-blind, randomised trial by Riker et al. in which 68 centres in 5 countries recruited intubated 366 patients to received moderate to light sedation with either dexmedetomidine or midazolam. All patients received daily arousal assessment.
Their primary end point was the percentage of time within the target sedation range (RASS score −2 to +1) and this did not differ between the two groups.
Looking at the secondary endpoints though make things a lot more interesting. Just before the beginning of the sedation period both groups had a similar prevalence of delirium. During study drug administration though, the effect of dexmedetomidine treatment on delirium was significant. A reduction of 24.9% with dexmedetomidine is rather impressive (see figure below). This effect was even greater in patients who were CAM-ICU-positive at baseline.
Finally patients on dexmedetomidine had shorter time to extubation (1.9 days in average) while their length of stay on ICU did not differ.
From a safety point of view the most common adverse effect of dexmedetomidine was bradycardia. It's noteworthy that patients on midazolam had more episodes of hypotension and tachycardia.
THE BOTTOM LINE
- This is another study indicating that dexmedetomidine seems to be beneficial in regards of delirium in mechanically ventilated patients and might speed up time to extubation
- Dexmedetomidine is safe in patients where moderate to light sedation is the aim
Riker et al. JAMA. 2009;301(5):489-499. doi:10.1001/jama.2009.56 OPEN ACCESS
Read more HERE on BIJC
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
Ketamine - a drug with various actions and just as many opinions on it. One concern often mentioned is that ketamine might cause a raise in intracranial pressure (ICP) and therefore is often avoided in this group of patients. In May's Journal of Anaesthesia Wang et al. looked at the existing evidence on this topic. They ended up with 5 trials meeting their inclusion criteria on administration of ketamine and the ICP levels within the first 24h as a primary outcome.
To make it short: Ketamine does not increase ICP in comparison to opioids. They conclude that ketamine should not be discouraged on the basis of ICP-related concerns.
Wang et al. J Anaesth. 2014 May 24
Since the FDA’s approval of Propofol in 1993 it has become one of the most important drugs used in anaesthesia. It’s properties (short induction time, short half life) have made it an ideal agent for the use in theatre. Also in critical care Propofol was increasingly used for long term sedation and it’s anti-epileptic properties have been welcomed by intensivists treating patients with status epilepticus. In 1992 T.J. Parke et al. published for the first time an article in the BMJ describing 5 children who developed increasing metabolic acidosis, brady-arrhythmia and progressive myocardial failure while sedated with Propofol - today often referred as the Propofol Infusion Syndrome (PRIS). This rare complication shows a complex pathophysiology which is still not fully understood and still continues to be controversially discussed.
While initially described in children and traumatic brain injury it is also increasingly reported in other critically ill patients. If you are interested in some background information on this syndrome this recent case report by Mayette et al., published in the Annals of Intensive Care, provides an interesting insight in this topic.
Parke et al. BMJ. 1992;305:613
Mayette M. et al. Ann Intensive Care. 2013 Sep 23;3(1):32
Take Home Message: Risk factors for PRIS appear to be...