OBJECTIVE Ketamine is an N-methyl-D-aspartate antagonist with emerging evidence assessing its use as a continuous infusion agent to provide concomitant analgesia and sedation. The role of ketamine as adjunctive therapy in mechanically ventilated patients is unclear. This study sought to investigate the impact of adjunctive continuous infusion ketamine on concomitant analgesic and sedative dosing while providing goal comfort in mechanically ventilated patients. METHODS This retrospective two-center intrapatient comparison study included mechanically ventilated adult ICU patients who received continuous infusion ketamine with at least one other analgesic or sedative infusion. The primary outcome assessed percent relative change in concomitant analgesic-sedative doses 24 hours after ketamine initiation. Secondary outcomes included percent of Richmond Agitation and Sedation Score (RASS) assessments at goal, adverse effects, and delirium incidence. Exploratory evaluation of independent factors associated with ketamine responders (50% or more relative reduction in analgesic-sedative dosing requirements at 24 hrs) and nonresponders (less than 50% relative reduction) was performed using multivariate logistic regression. RESULTS Overall, 104 patients were included. A total of 160 concomitant analgesic-sedative infusions were used in combination with ketamine, most commonly fentanyl (98 [61.3%]) and propofol (46 [28.8%]). A 20% (interquartile range [IQR] -63.6 to 0.0, p<0.001) relative reduction in total analgesic-sedative infusion pharmacotherapy was achieved at 24 hours after ketamine initiation. Analgesic and sedative infusion doses decreased at 24 hours (fentanyl: pre, 175 μg/hr [IQR 100-200 μg/hr] vs post, 125 μg/hr [IQR 50-200 μg/hr], p<0.001; propofol: pre, 42.5 μg/kg/min [IQR 20.0-60.0 μg/kg/min] vs post, 20.0 μg/kg/min [IQR 3.8-31.3 μg/kg/min], p<0.001). Median percent time within goal RASS improved after ketamine initiation (pre, 7.1% [0-40%] vs post, 25% [0-66.7%], p=0.005). No differences were observed in secondary outcomes between responders and nonresponders, except a longer non-ICU hospital length of stay in responders. Independent factors associated with ketamine response included a lower body mass index, higher starting dose of ketamine, lower severity of illness, and need for multiple concomitant analgesic-sedative infusions before initiation of ketamine. CONCLUSIONS Adjunctive continuous infusion ketamine promotes analgesic and sedative dose-sparing effects in mechanically ventilated patients while improving time spent within goal sedation range. Further prospective research is warranted.

Continuous Infusion Ketamine for Adjunctive Analgosedation in Mechanically Ventilated, Critically Ill Patients.

Ketamine sedation in mechanically ventilated patients: A systematic review and meta-analysis.

Objective: The aim of this study was to synthesize evidence available on continuous infusion ketamine versus nonketamine regimens for analgosedation in critically ill patients. Data sources A search of MEDLINE, EMBASE, CINAHL, CDSR, and ClinicalTrials.gov was performed from database establishment to November 2021 using the following search terms: critical care, ICU, ketamine, sedation, and anesthesia. All studies included the primary outcome of interest: daily opioid and/or sedative consumption. Study selection and data extraction Relevant human studies were considered. Randomized controlled trials (RCT), quasi-experimental studies, and observational cohort studies were eligible. Two reviewers independently screened articles, extracted data, and appraised studies using the Cochrane RoB and ROBINS-I tools. Data synthesis A total of 13 RCTs, 5 retrospective, and 1 prospective cohort study were included (2255 participants). The primary analysis of six RCTs demonstrated reduced opioid consumption with ketamine regimens (n = 494 participants, −13.19 µg kg−1 h−1 morphine equivalents, 95% CI −22.10 to −4.28, P = 0.004). No significant difference was observed in sedative consumption, duration of mechanical ventilation (MV), ICU or hospital length of stay (LOS), intracranial pressure, and mortality. Small sample size of studies may have limited ability to detect true differences between groups. Relevance to patient care and clinical practice This meta-analysis examining ketamine use in critically ill patients is the first restricting analysis to RCTs and includes up-to-date publication of trials. Findings may guide clinicians in consideration and dosing of ketamine for multimodal analgosedation. Conclusion Results suggest ketamine as an adjunct analgosedative has the potential to reduce opioid exposure in postoperative and MV patients in the ICU. More RCTs are required before recommending routine use of ketamine in select populations.

https://journals.sagepub.com/doi/pdf/10.1177/10600280211069617

Impact of Ketamine on Analgosedative Consumption in Critically Ill Patients: A Systematic Review and Meta-Analysis

Abstract Aim This systematic review aimed to investigate the drugs used and their potential effect on noninvasive ventilation (NIV). Background NIV is used increasingly in acute respiratory failure (ARF). Sedation and analgesia are potentially beneficial in NIV, but they can have a deleterious impact. Proper guidelines to specifically address this issue and the recommendations for or against it are scarce in the literature. In the most recent guidelines published in 2017 by the European Respiratory Society/American Thoracic Society (ERS/ATS) relating to NIV use in patients having ARF, the well-defined recommendation on the selective use of sedation and analgesia is missing. Nevertheless, some national guidelines suggested using sedation for agitation. Methods Electronic databases (PubMed/Medline, Google Scholar, and Cochrane library) from January 1999 to December 2019 were searched systematically for research articles related to sedation and analgosedation in NIV. A brief review of the existing literature related to sedation and analgesia was also done. Review results Sixteen articles (five randomized trials) were analyzed. Other trials, guidelines, and reviews published over the last two decades were also discussed. The present review analysis suggests dexmedetomidine as the emerging sedative agent of choice based on the most recent trials because of better efficacy with an improved and predictable cardiorespiratory profile. Conclusion Current evidence suggests that sedation has a potentially beneficial role in patients at risk of NIV failure due to interface intolerance, anxiety, and pain. However, more randomized controlled trials are needed to comment on this issue and formulate strong evidence-based recommendations. How to cite this article Karim HMR, Šarc I, Calandra C, Spadaro S, Mina B, Ciobanu LD, et al. Role of Sedation and Analgesia during Noninvasive Ventilation: Systematic Review of Recent Evidence and Recommendations. Indian J Crit Care Med 2022;26(8):938–948.

/pdf/role-of-sedation-and-analgesia-during-noninvasive-rgrrwn9f.pdf

Role of Sedation and Analgesia during Noninvasive Ventilation: Systematic Review of Recent Evidence and Recommendations

Noninvasive ventilation (NIV) is increasingly used in acute respiratory failure in order to avoid complications related to invasive mechanical ventilation. Patient’s compliance is essential to its success, therefore sedative and/or analgesic drugs could be potentially used to reduce discomfort and risk of NIV failure in selected patients. Although sedation and analgesia have a potentially beneficial and even deleterious role, guidelines to specifically address this issue and recommend for or against is relatively missing. Even in the most recent clinical practice guidelines by ERS/ATS for the use of NIV for ARF published in 2017, guidance on sedation and analgesia is missing. Electronic databases (Google Scholar, PubMed, and Cochrane Library) from 2017 to 2019 were searched to find out the recent literature related to sedation in noninvasive ventilation. In this chapter, a brief review of the literature and analysis of the studies related to sedation and analgesia were also done.

Role of Sedation and Analgesia During Noninvasive Ventilation

Background:At this time, there are no studies evaluating the risk of delirium or coma with the use of ketamine in mechanically ventilated adult patients, compared to conventional therapies such as ...

Comparison of Ketamine- Versus Nonketamine-Based Sedation on Delirium and Coma in the Intensive Care Unit:

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Current evidence supports the use of symptom-triggered therapy for alcohol withdrawal syndrome (AWS). Early, escalating therapy appears to decrease ICU length of stay (LOS); however, the effect of this approach on hospital LOS remains unknown. The hypothesis of this study is that focused benzodiazepine (BZD) treatment in the first 24 hours after recognition of AWS will decrease overall hospital LOS. Methods: This pre-post cohort study was conducted in adult patients with severe AWS at an academic medical center. The preintervention cohort (PRE) was admitted between January 2015 and November 2015. The post-intervention cohort (POST) was admitted between April 2016 and March 2017. Severe AWS was defined as patients requiring diazepam doses of > 30 mg. Focused treatment was defined as > 50% of total diazepam usage within the first 24 hours of recognition of AWS. In the PRE group, patients received symptom-triggered, escalating doses of diazepam and phenobarbital based on their Richmond Agitation-Sedation Scale (RASS). In the POST group, patients were treated using a revised and time-limited course of therapy. Escalating doses of BZD and phenobarbital were given during a 24 hour loading phase and all therapy was discontinued automatically at 4 days from AWS recognition. In addition to the symptom triggered therapy for agitation (RASS), the SHOT scale was used to assess non-agitation symptoms of AWS and direct additional doses of diazepam. The primary outcome was hospital LOS; secondary outcomes included ICU LOS, BZD use, and ventilator-free days. Results: 532 patients were treated using the AWS protocol; 113 experienced severe AWS. The PRE (n = 75) and POST (n = 38) groups were evenly matched in age, sex, history of AWS, and severity of illness. There was a substantial difference in POST patients who received focused treatment, 51.3% vs. 73.7%, p = 0.03. The POST group had a significant decrease in hospital LOS (14.0 vs. 9.8 days, p = 0.03) and ICU LOS (7.4 vs. 4.4 days, p = 0.03). Conclusions: Early and focused management of severe AWS was associated with a decrease in ICU and hospital LOS.

958: delirium and coma-free days in patients receiving continuous- infusion ketamine versus propofol

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Comparison of Ketamine- Versus Nonketamine-Based Sedation on Delirium and Coma in the Intensive Care Unit:

958: delirium and coma-free days in patients receiving continuous- infusion ketamine versus propofol