It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock.OBJECTIVE To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTSMulticenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019.INTERVENTIONS Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. MAIN OUTCOMES AND MEASURESThe primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality.RESULTS Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported. CONCLUSIONS AND RELEVANCEIn patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone.

Testing for malignant hyperthermia in New Zealand involves two tests-in vitro contracture testing of excised lateral quadriceps muscle and DNA analysis. In vitro contracture testing is regarded as the gold standard in malignant hyperthermia diagnosis but several publications have questioned the reliability of a normal result. Analysis of 479 anaesthetic records in 280 patients or their descendants throughout New Zealand who had tested negative for malignant hyperthermia, demonstrated there was no evidence of malignant hyperthermia episodes in this group who had been administered anaesthetic triggering agents. A wide range of anaesthetics were used over the study period. Analysis of each anaesthetic record was undertaken using the malignant hyperthermia grading scale which determines the likelihood that an anaesthetic event represents a malignant hyperthermia episode. Confirmation of the negative results was further supported by normal DNA analysis of patients in 48% of anaesthetics. There are advantages to using inhalational agents in certain situations and although demonstrating a zero risk of a malignant hyperthermia episode is not statistically possible, evidence in this large series suggests that the risk of an episode in these patients is extremely low and may be negligible. We suggest that anaesthetic triggering agents can be used safely in patients with normal in vitro contracture tests, and in their descendants.

We conducted a survey of Australian and New Zealand anaesthetists designed to quantify self-reported use of cricoid pressure (CP) in patients presumed to be at risk of gastric regurgitation, and to ascertain the underlying justifications used to support individual practice. We aimed to identify the perceived benefits and harms associated with the use of CP and to explore the potential impact of medicolegal concerns on clinical decision-making. We also sought to ascertain the views of Australian and New Zealand anaesthetists on whether recommendations relating to CP should be included in airway management guidelines. We designed an electronic survey comprised of 15 questions that was emailed to 981 randomly selected Fellows of the Australian and New Zealand College of Anaesthetists (ANZCA) by the ANZCA Clinical Trials Network on behalf of the investigators. We received responses from 348 invitees (response rate 35.5%). Of the 348 respondents, 267 (76.9%) indicated that they would routinely use CP for patients determined to be at increased risk of gastric regurgitation. When asked whether participants believed the use of CP reduces the risk of gastric regurgitation, 39.8% indicated yes, 23.8% believed no and 36.3% were unsure. Of the respondents who indicated that they routinely performed CP, 159/267 (60%) indicated that concerns over the potential medicolegal consequences of omitting CP in a patient who subsequently aspirates was one of the main reasons for using CP. The majority (224/337; 66%) of respondents believed that recommendations about the use of CP in airway management guidelines should include individual practitioner judgement, while only 55/337 (16%) respondents believed that routine CP should be advocated in contemporary emergency airway management guidelines.