Acute and Critical Care

Review Article

Meta-analysis
The impact of ketamine on outcomes in critically ill patients: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials: Yerkin Abdildin, Karina Tapinova, Assel Nemerenova, Dmitriy Viderman; Acute Crit Care. 2024;39(1):34-46. Published online February 28, 2024; DOI: https://doi.org/10.4266/acc.2023.00829

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Abstract PDF: Background
This meta-analysis aims to evaluate the effects of ketamine in critically ill intensive care unit (ICU) patients.
Methods
We searched for randomized controlled trials (RCTs) in PubMed, Scopus, and the Cochrane Library; the search was performed initially in January but was repeated in December of 2023. We focused on ICU patients of any age. We included studies that compared ketamine with other traditional agents used in the ICU. We synthesized evidence using RevMan v5.4 and presented the results as forest plots. We also used trial sequential analysis (TSA) software v. 0.9.5.10 Beta and presented results as TSA plots. For synthesizing results, we used a random-effects model and reported differences in outcomes of two groups in terms of mean difference (MD), standardized MD, and risk ratio with 95% confidence interval. We assessed the risk of bias using the Cochrane RoB tool for RCTs. Our outcomes were mortality, pain, opioid and midazolam requirements, delirium rates, and ICU length of stay.
Results
Twelve RCTs involving 805 ICU patients (ketamine group, n=398; control group, n=407) were included in the meta-analysis. The ketamine group was not superior to the control group in terms of mortality (in five studies with 318 patients), pain (two studies with 129 patients), mean and cumulative opioid consumption (six studies with 494 patients), midazolam consumption (six studies with 304 patients), and ICU length of stay (three studies with 270 patients). However, the model favored the ketamine group over the control group in delirium rate (four studies with 358 patients). This result is significant in terms of conventional boundaries (alpha=5%) but is not robust in sequential analysis. The applicability of the findings is limited by the small number of patients pooled for each outcome.
Conclusions
Our meta-analysis did not demonstrate differences between ketamine and control groups regarding any outcome except delirium rate, where the model favored the ketamine group over the control group. However, this result is not robust as sensitivity analysis and trial sequential analysis suggest that more RCTs should be conducted in the future.

Original Article

The Effects of Intrathecal Ketamine and NBQX on Neurologic Injury and Spinal Cord Glutamate Receptor mRNA Expression in Transient Spinal Ischemia in the Rat: Seung Hoon Baek, Jung Min Hong, Kyoo Sub Chung; Korean J Crit Care Med. 2005;20(1):24-31.

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Abstract PDF: BACKGROUND
Spinal cord injury occurring as the result of surgical repair of thoracic and thoracoabdominal aortic disease remains a devastating complication. Excitatory amino acids have been known to cause neurologic injury after neuronal ischemia. The purpose of this study was to elucidate the effects of intrathecal ketamine or NBQX on neurologic outcome and NMDA receptor gene expression in transient spinal ischemia. METHODS: Sprague-Dawley rats were anesthetized with enflurane, divided by 4 groups: Control (C group), Intrathecal ketamine 0.1 mg (K-1 group), Intrathecal ketamine 0.2 mg (K-2 group), and intrathecal NBQX 1 nM (N group). Spinal ischemia was produced by both induced hypotension and thoracic aortic cross clamping. After spinal ischemia, neurologic scores were assessed after 1, 2, 3 hours. After 3 hours rats were euthenized and spinal cords were removed for the assay of NMDAR and mGlu1 mRNA. RESULTS: The neurol ogic scores of K-2 and N groups were significantly lower than C group and K-1 group. There were no significant difference between K-1 group and C group. The NMDAR and mGlu1 gene expression was increase in C and K-1 group compared to sham operation. In K-2 and N groups, the gene expressions were significantly lesser than C group.
CONCLUSIONS
The NMDAR and mGlu1 gene expressions were increased in transient spinal ischemia. Intrathecal ketamine and NBQX were effective in preventing neurologic injury after transient spinal ischemia. The NMDA antagonistic action of ketamine might involve to prevent neurologic injury.

Case Report

Continuous Infusion of Ketamine in Mechanically Ventilated Patient in Septic Shock with Status Asthmaticus: Bon Nyeo Koo, Shin Ok Koh, Sung Yong Park, Jae Kwang Shim, Sung Sik Chon; Korean J Crit Care Med. 2000;15(2):108-112.

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Abstract PDF: Ketamine is well known for its analgesic, bronchodilating and sympathetic stimulating effect. Hence, it has been widely used for induction of patients with hypotension or asthma and also for analgesic and sedating purposes in the ICU. We presented a 62 year old female patient with ventilator support in septic shock with refractory asthma whom we managed successfully with continuous intravenous infusion of ketamine postoperatively in the ICU. The patient had a history of asthma but had been asymptomatic recently and was scheduled for an emergent explo-laparotomy under the diagnosis of acute panperitonitis. Before the induction of anesthesia, the patient was in septic shock but no wheezing could be auscultated. After the induction of general anesthesia and endotracheal intubation, wheezing was apparent in both lung fields with a high peak inspiratory pressure. Inotropics, vasopressors and bronchodilators were promptly instituted without any improvement of asthma and the patient had to be transferred to the ICU with intubated after the operation. Clinical symptoms of asthma continued throughout the first day despite using bronchodilators under mechanical ventilation but, after starting the IV infusion of ketamine, there were decrease in the peak inspiratory pressure and wheezing with a subsequent improvement in the arterial blood gas analysis findings. We could also achieve considerable analgesic and sedating effect without any decrease in the blood pressure. The patient's general physical status improved and weaning with extubation was successfully done on the 21st day and was transferred to the general ward on the 28th day.

Randomized Controlled Trial

Comparison of the Efficacy between Ketamine and Morphine on Sedation and Analgesia in Patients with Mechanical Ventilation: Tae Hyung Kim, Chae Man Lim, Tae Sun Shim, Sang Do Lee, Woo Sung Kim, Dong Soon Kim, Won Dong Kim, Younsuck Koh; Korean J Crit Care Med. 2000;15(2):82-87.

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Abstract PDF: BACKGROUND
While the combination therapy of morphine and benzodiazepine has been recommended as a standard therapy for sedation and analgesia in patients with mechanical ventilation, morphine can suppress respiratory center, and also decrease blood pressure and bowel movement. Because ketamine has analgesic and sedative effects compatible to morphine without depression of the cardiovascular and respiratory systems in addition to the preservation of bowel activity, ketamine may substitute morphine. However, it has not well known such potential advantages of ketamine in patients with mechanical ventilation.
METHODS
Thirty eight patients (male:female=30:8, age=62.6 +/- 11.7 years) with mechanical ventilation were randomized as ketamine and morphine group (n=21 vs. n=17). There was no significant differences in sex, age and APACHE III score at the initiation of mechanical ventilation (ketamine group, morphine group: 79.4 +/- 2.0, 82.0 +/- 20.6). The study duration was 24 h after drug administration and minimum dose, which maintains ventilator-patient synchrony or the status of Ramsay score 3, was used. Ramsay sedation score, hemodynamic variables, respiratory and arterial blood gas variables, and bowel sound were measured at every 4 h. Arterial blood gas analysis was checked at 0, 4, and 24 h.
RESULTS
1) There were no significant differences in Ramsay sedation score and other hemodynamic, respiratory, and arterial blood gas variables in each group. The dose of combined midazolam was not different between two groups (ketamine vs. morphine; 52.1 +/- 11.9 vs. 46.7 +/- 15.1 mg/d; p=0.23). 2) The cases with decreased mean arterial pressure over 25% of the baseline shortly after the drug administration less frequently observed in ketamine group, although the difference did not reach statistical significance (n=2, 9.5% vs. n=5, 29.4%; p=0.12). 3) Bowel movement reduction at 4 h after the drug administration was less in ketamine group (n=1, 4.8% vs. n=6, 35.3%, p=0.03). The difference was not observed at 8 h. 4) Cost of the drug for 24 h was more expensive in ketamine group (dose & cost; 688 506 mg/d & 25,891 7,743 won vs. 40 +/- 18 mg/d, 15,814 +/- 4,853 won; p<0.001).
CONCLUSIONS
Considering the advantages in the hemodynamics and bowel movement, ketamine may substitute morphine for the sedation of patients with mechanical ventilation, if indicated.

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