3Analgesia, sedation, and neuromuscular blockade during targeted temperature management after cardiac arrest
Section snippets
Therapeutic goals during TTM
Among general intensive care unit (ICU) patients, the primary goals when providing sedation vary based on patient severity of illness, particular injuries or diseases, and specific therapies being administered. In 2013, the most recent guidelines for treating ICU pain, agitation, and delirium (PAD) were published, including 472 references and >50 recommendations [5]; unfortunately, the practice of TTM was not included in these PAD guidelines. Light sedation was strongly recommended because of
Comfort
Comfort for ICU patients is an important and likely universally accepted goal. Despite this, 26% of TTM reports did not list any analgesic medication during TTM [3], which may not always mean none was given, but could reflect that practice. Among the studies reporting analgesic drugs and doses administered during TTM, fentanyl was the most common medication, and doses varied widely, from 0.5 to 10 μg/kg/h (equivalent to 40–800 μg/h for an 80-kg adult) with an estimated median dose of
Challenges for sedation, analgesia, and NMB during TTM
Many aspects of TTM practice add complexity when clinicians try to define a best approach to sedation, analgesia, and neuromuscular blockade; temperature target is among these. Though no longer uniformly used as a target since the TTM trial was published [33], hypothermia at 33 °C has a major and complex effect on drug metabolism mediated by blood flow changes, specific hepatic metabolism pathway, degree of renal excretion, and protein binding and distribution ∗[8], ∗[46], [47]. Besides
Specific medications
Regarding the choice of medications for providing sedation, analgesia, and NMB during TTM, very little comparative research has taken place. Clinical practice guidelines for post-resuscitation cardiac arrest care offer little guidance on which medications should be used during TTM, and which outcomes relative to these drugs should be reported, leading to a wide practice variation ∗[3], [12], [54]. It is unknown whether standardizing sedation, analgesia, and NMB may influence important outcomes
Minimizing adverse events with monitoring
Sedation during TTM is a challenging issue. In an effort to insure adequate analgesia and comfort, we know that clinicians frequently overshoot the target level of sedatives and analgesics ∗[5], [38]. For the vast majority of ICU patients, deep sedation may delay extubation ∗[5], [38], [39], [40], ICU transfer ∗[5], [38], [40], lead to an increased incidence of delirium [5], or confound neurological assessment, perhaps leading to inappropriate withdrawal of life support ∗[1], [2], ∗[76]. In
Summary
TTM has revolutionized post-cardiac arrest care, with significantly improved outcomes for initial survivors with hypoxic–ischemic encephalopathy. Many aspects of this therapy require further study, including the approach to sedation, analgesia, and NMB. Evidence confirms that midazolam accumulates significantly with continuous infusion, and hypothermia greatly delays midazolam clearance, resulting in delayed wakening. More than just an inconvenience, delayed wakening is known to confound
Conflict of interest
Dr. Riker reports that equipment support for sedation research was received from Aspect Medical Systems and from Hospira for multicenter dexmedetomidine research.
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Cited by (18)
Validation of the suppression ratio from a simplified EEG montage during targeted temperature management after cardiac arrest
2020, ResuscitationCitation Excerpt :Several limitations of our study warrant comment. These data were collected in a single institution using a moderate sedation protocol19 in a relatively small cohort of patients who were monitored for hours but the duration of epochs compared was brief. To reduce bias, we blinded investigators to MSR data while PSR data was being calculated, to PSR data while MSR data was later calculated, and the EEG background and aEEG patterns were scored with both SR values masked, but patients were openly monitored with both EEG technologies.
Late awakening, prognostic factors and long-term outcome in out-of-hospital cardiac arrest – results of the prospective Norwegian Cardio-Respiratory Arrest Study (NORCAST)
2020, ResuscitationCitation Excerpt :Consequently, some EEG patterns classified as grade 4 would not have been regarded malignant by newer classification.29 Sedation regimen affect time to awakening and WLST,33 and was highlighted as a knowledge gap in the 2014 ERC/ESICM advisory statement.13 Our sedation protocol recommended propofol/fentanyl in stable patients, but the majority were deeply sedated (RASS 5) with midazolam/fentanyl (Table A1, ASM).
Continuous surface EMG power reflects the metabolic cost of shivering during targeted temperature management after cardiac arrest
2018, ResuscitationCitation Excerpt :We monitored patients during the maintenance phase of TTM, which may not apply during the induction or rewarming phases. Our study evaluated a convenience sample of 18 patients from a single center, targeting 33 °C, and embracing a moderate intensity sedation and analgesia approach to TTM [13,14]. Potential enrollment bias may have affected our outcomes, and data may differ with more intensive sedation or different temperature targets.
Neuromuscular Blockade in the 21st Century Management of the Critically Ill Patient
2017, ChestCitation Excerpt :Shivering is a consequence of therapeutic hypothermia, which leads to heat production, increased metabolic rate, inflammation, increased ICP, decreased brain tissue oxygen levels, and muscle soreness. Both opioids and NMBAs may be used to reduce shivering; however, the ideal combination of agents and dosing strategy remains unclear.47 Furthermore, hypothermia induces alterations in both the pharmacodynamics and pharmacokinetics of these medications and blunts train-of-four (TOF) monitoring of paralysis depth, which further complicates management.48,49
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