Ketamine as adjunctive or monotherapy for post-intubation sedation in patients with trauma on mechanical ventilation: A rapid review.

Background: The effectiveness of ketamine as adjunctive or monotherapy for post-intubation sedation in adults with trauma on mechanical ventilation is unclear. Methods: A rapid review of systematic reviews of randomized controlled trials, then randomized controlled trials or observational studies was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on June 1, 2022. We used a prespecified protocol following Cochrane rapid review methods. Results: We identified eight systematic reviews of randomized controlled trials and observational studies. Among the included reviews, only the most relevant, up to date, highest quality-assessed reviews and reviews that reported on critical outcomes were considered. Adjunctive ketamine showed a morphine sparing effect (MD -13.19 µmg kg-1 h-1, 95 % CI -22.10 to -4.28, moderate certainty of evidence, 6 RCTs), but no to little effect on midazolam sparing effect (MD 0.75 µmg kg-1 h-1, 95 % CI -1.11 to 2.61, low certainty of evidence, 6 RCTs) or duration of mechanical ventilation in days (MD -0.17 days, 95 % CI -3.03 to 2.69, moderate certainty of evidence, 3 RCTs).Adjunctive ketamine therapy may reduce mortality (OR 0.88, 95 % CI 0.54 to 1.43, P = 0.60, very low certainty of evidence, 5 RCTs, n = 3076 patients) resulting in 30 fewer deaths per 1000, ranging from 132 fewer to 87 more, but the evidence is very uncertain. Ketamine results in little to no difference in length of ICU stay (MD 0.04 days, 95 % CI -0.12 to 0.20, high certainty of evidence, 5 RCTs n = 390 patients) or length of hospital stay (MD -0.53 days, 95 % CI -1.36 to 0.30, high certainty of evidence, 5 RCTs, n = 277 patients).Monotherapy may have a positive effect on respiratory and haemodynamic outcomes, however the evidence is very uncertain. Conclusion: Adjunctive ketamine for post-intubation analgosedation results in a moderate meaningful net benefit but there is uncertainty for benefit and harms as monotherapy.

Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review.

BACKGROUND: Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice. OBJECTIVE: To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults. METHODS: A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12 February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines. RESULTS: We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151 735 participants), resulting in 15 more per 1 000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09 - 6.80; low certainty of evidence; four observational studies, n=167 847 participants), resulting in 45 more per 1 000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews or trials. CONCLUSION: Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects.

Respiratory presentations to acute services at a tertiary hospital in South Africa.

BACKGROUND: Respiratory diseases account for >10% of the global burden of disease when measured in disability-adjusted life-years. The burden of chronic respiratory diseases (CRDs) increases as the world's population ages, with a much greater increase in low- to middle-income countries. OBJECTIVES: To characterise and quantify the reasons for acute respiratory presentations to the acute care services at a tertiary hospital in Cape Town, South Africa. METHODS: A cross-sectional descriptive study was conducted. Casualty registers and electronic record databases were reviewed to determine the diagnoses of consecutive patients attending the casualty unit from May 2019 to January 2020. RESULTS: A total of 1 053 individual patients presented with a primary respiratory diagnosis. Fewer than 10% of admissions were from outside the Cape Town metropole, while >60% were from the subdistrict immediately adjacent to the hospital. Of all patients, 8.3% were readmitted at least once within the 9-month study period. Six hundred and forty-three (61.1%) of the patients presented with non-CRDs. The main reasons for presentation in these patients were pulmonary tuberculosis (PTB) (n=224; 21.3%), other infections including lower respiratory tract infections, pneumonia and bronchitis (n=272; 25.8%), and cancer (n=140; 13.3%). Haemoptysis was seen in 9.8% of all patients, mainly explained by post-tuberculosis lung disease (PTLD) (37.9%) and PTB (36.9%). Of the patients, 410 (38.9%) had an underlying CRD, with chronic pulmonary obstructive disease (COPD) being the most common (n=192; 18.2%), followed by PTLD (n=88; 8.5%) and asthma (n=52; 5.1%). CONCLUSIONS: Over a 9-month period, acute respiratory presentations to a tertiary hospital were mainly for primary/secondary level of care indications, highlighting disparity in accessing tertiary services. COPD and PTLD predominated among CRDs, while infections and cancers were common. A high readmission rate was found for several diseases, suggesting the potential for targeted interventions to prevent both admissions and readmissions and reduce acute hospital utilisation costs.

Comparison of patients with severe COVID-19 admitted to an intensive care unit in South Africa during the first and second wave of the COVID-19 pandemic.

Background: The second wave of coronavirus disease 2019 (COVID-19), dominated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant, has been reported to be associated with increased severity in South Africa (SA). Objectives: To describe and compare clinical characteristics, management and outcomes of COVID-19 patients admitted to an intensive care unit (ICU) in SA during the first and second waves. Methods: In a prospective, single-centre, descriptive study, we compared all patients with severe COVID-19 admitted to ICU during the first and second waves. The primary outcomes assessed were ICU mortality and ICU length of stay (LOS). Results: In 490 patients with comparable ages and comorbidities, no difference in mortality was demonstrated during the second compared with the first wave (65.9% v. 62.5%, p=0.57). ICU LOS was longer in the second wave (10 v. 6 days, p<0.001). More female admissions (67.1% v. 44.6%, p<0.001) and a greater proportion of patients were managed with invasive mechanical ventilation than with non-invasive respiratory support (39.0% v. 14%, p<0.001) in the second wave. Conclusion: While clinical characteristics were comparable between the two waves, a higher proportion of patients was invasively ventilated and ICU stay was longer in the second. ICU mortality was unchanged.