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

Shurtleff, Vanessa; Radosevich, John; Patanwala, Asad E.

doi:10.1177/0885066618767619

Cited by 27 publications

(55 citation statements)

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“…Important to note with an improved time in goal sedation range, no difference was observed in delirium incidence 24 hours before versus after ketamine initiation, although only 57 patients had complete documentation of CAM‐ICU status and were included in the total analysis. This observation aligns with published data that found an incidence of delirium in 29 (74%) patients with ketamine‐based sedation regimens versus 34 (85%) patient on non–ketamine‐based regimens (p=0.274) …”

Section: Discussionsupporting

confidence: 92%

“…This observation aligns with published data that found an incidence of delirium in 29 (74%) patients with ketamine-based sedation regimens versus 34 (85%) patient on non-ketamine-based regimens (p=0.274). 26 We chose to report a qualitative assessment of vasopressor dosing requirements after ketamine initiation instead of a quantitative assessment. The results suggest that ketamine did not negatively affect hemodynamics and may actually supplement vasopressor weaning efforts, although this could not be comparatively assessed given lack of a control group.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…The development of the emergence phenomenon can cause patients to transiently require higher amounts of other sedatives, usually benzodiazepines. However, ketamine-based analgo-sedation in MV patients administered as a subanesthetic/sub-dissociative/low dose results in similar numbers of delirium-and coma-free days as those in non-ketamine-based regimens, as shown in a retrospective cohort study conducted by Shurtleff et al at an academic medical center [8]. Ketamine infusion in this trial was 5 μ g/ kg/min (0.3 mg/kg/h) titrated using 5 μ g/kg/min every 5 min up to a maximum of 25 μ g/kg/min (1.5 mg/kg/h).…”

Section: Introductionmentioning

confidence: 74%

“…The incidence of side effects (i.e., nausea, delirium, hallucination, hypoventilation, pruritus, and sedation) did not differ between the ketamine and opioidalone groups. Based on this generally positive ICU RCT, the 2018 PADIS panel made a conditional recommendation for the use of low-dose ketamine as an adjunct to opioids to optimize acute post-operative pain management in critically ill adults (refer to Supplementary Table 1: Previous ketamine trials in the ICU setting) [2][3][4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…However, most patients in the ICU are sedated with a combination of drugs. Moreover, most trials had a limited focus on patientcentered outcomes, such as duration of MV or ICU LOS, as the primary outcome favoring surrogate outcomes, such as sedation scores and changes in analgesics and sedatives [2][3][4][5][6][7][8][9][10][11]. To help further delineate ketamine's role as a maintenance analgo-sedation agent in the ICU, further RCTs need to be conducted to compare the effects of ketamine to those of other analgesics and sedatives on reducing the duration of MV, ICU LOS, and delirium occurrence.…”

Section: Introductionmentioning

confidence: 99%

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Adjunct low-dose ketamine infusion vs standard of care in mechanically ventilated critically ill patients at a Tertiary Saudi Hospital (ATTAINMENT Trial): study protocol for a randomized, prospective, pilot, feasibility trial

Bawazeer

Amer

Maghrabi

et al. 2020

Trials

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Background: A noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption guideline suggested low-dose ketamine infusion as an adjunct to opioid therapy to reduce opioid requirements in post-surgical patients in the intensive care unit (ICU). This was, however, rated as conditional due to the very low quality of evidence. Ketamine has favorable characteristics, making it an especially viable alternative for patients with respiratory and hemodynamic instability. The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care in critically ill patients on mechanical ventilation (MV) for ≥ 24 h.Methods/design: This trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult ICU patients (> 14 years old) on MV. The study will take place in the adult ICUs in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia, and will enroll 80 patients. Patients will be randomized postintubation into two groups: the intervention group will receive an adjunct low-dose continuous infusion of ketamine plus standard of care. Ketamine will be administered over a period of 48 h at a fixed infusion rate of 2 μg/ kg/min (0.12 mg/kg/h) in the first 24 h followed by 1 μg/kg/min (0.06 mg/kg/h) in the second 24 h. The control group will receive standard of care in the ICU (propofol and/or fentanyl and/or midazolam) according to the KFSH&RC sedation and analgesia protocol as clinically appropriate. The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first.

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Comparison of Hydromorphone versus Fentanyl‐based Sedation in Extracorporeal Membrane Oxygenation: A Propensity‐Matched Analysis

et al. 2020

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INTRODUCTION Data comparing sedatives in patients receiving extracorporeal membrane oxygenation (ECMO) are sparse. However, it is known that the ECMO circuit alters the pharmacokinetic properties of medications via drug sequestration of lipophilic agents and increased volume of distribution. OBJECTIVES This study evaluated the difference in days alive without delirium or coma and the sedative requirements in patients receiving fentanyl versus hydromorphone in ECMO patients. METHODS This single-center retrospective observational study evaluated adults receiving ECMO for more than 48 hours and continuous infusion of either fentanyl or hydromorphone for at least 6 hours. Of 148 patients evaluated, 88 received fentanyl and 60 received hydromorphone continuous infusion sedation. Outcomes included delirium-free and coma-free (DFCF) days, narcotic use, and sedative use. MAIN RESULTS There was an increase in the number of DFCF days in the hydromorphone group at day 7 (p=0.07) and day 14 (p=0.08) and a significant reduction in daily fentanyl equivalent exposure. Propensity score matching yielded 54 matched pairs. An 11.1% increase was observed in the proportion of ECMO days alive without delirium or coma in the hydromorphone group at 7 days (53.2% vs 42.1%, p=0.006). Patients in the hydromorphone group received significantly fewer narcotics with a median of 555 µg (interquartile range [IQR] 287-905 µg) of fentanyl equivalents per day compared with 2291 µg (IQR 1053-4023 µg) in the fentanyl group (p<0.005). CONCLUSION The use of hydromorphone-based sedation in ECMO patients resulted in more days alive without delirium or coma while significantly reducing narcotic requirements. KEY WORDS acute respiratory distress syndrome, extracorporeal membrane oxygenation, intensive care, sedation, delirium.

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

Abstract: Sustained ketamine-based sedation in mechanically ventilated patients may be associated with a higher rate of observed coma but similar delirium- and coma-free days compared nonketamine-based regimens.

Cited by 27 publications

References 13 publications

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

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

Adjunct low-dose ketamine infusion vs standard of care in mechanically ventilated critically ill patients at a Tertiary Saudi Hospital (ATTAINMENT Trial): study protocol for a randomized, prospective, pilot, feasibility trial

Comparison of Hydromorphone versus Fentanyl‐based Sedation in Extracorporeal Membrane Oxygenation: A Propensity‐Matched Analysis

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