Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial.

Importance: 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 Participants: Multicenter, 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 Measures: The 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], 76.3-145.4 hours) 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 Relevance: In 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03333278.

Oxygen therapy in acute resuscitation.

PURPOSE OF REVIEW: Avoidance and treatment of hypoxaemia is a cornerstone of acute resuscitation and yet the optimal approach to oxygen therapy in the acute care setting is uncertain. The aim of this review is to appraise recent evidence relating to the provision of supplemental oxygen to adult patients with acute illnesses with a focus on the resuscitation phase. RECENT FINDINGS: Recent findings generally support the notion that exposure to hyperoxaemia is associated with adverse outcomes in acutely ill adults with a range of diseases and raise the possibility that liberal provision of oxygen may cause harm. Several ongoing multicentre randomized trials aim to assess the effects of different oxygen therapy regimens on patient outcomes to provide a foundation for evidence-based recommendations regarding the use of supplemental oxygen in Intensive Care Unit patients. SUMMARY: At present, evidence is lacking to support routine liberal oxygen administration in acutely ill patients and, in most circumstances, a reasonable approach is to titrate supplemental oxygen to achieve an arterial oxygen saturation measured by pulse oximetry (SpO2) of 92-96% with the aim of avoiding both hypoxaemia and hyperoxaemia.

Associations between the intraoperative fraction of inspired intraoperative oxygen administration and days alive and out of hospital after surgery.

Background: There is limited knowledge about the effect of liberal intraoperative oxygen on non-infectious complications and overall recovery from surgery. Methods: In this retrospective cohort study, we investigated associations between mean intraoperative fraction of inspired oxygen (FiO2), and outcome in adults undergoing elective surgery lasting more than 2 h at a large metropolitan New Zealand hospital from 2012 to 2020. Patients were divided into low, medium, and high oxygen groups (FiO2 ≤ 0.4, 0.41-0.59, ≥0.6). The primary outcome was days alive and out of hospital at 90 days (DAOH90). The secondary outcomes were post-operative complications and admission to the ICU. Results: We identified 15,449 patients who met the inclusion criteria. There was no association between FiO2 and DAOH90 when high FiO2 was analysed according to three groups. Using high FiO2 as the reference group there was an adjusted mean (95% confidence interval [CI]) difference of 0.09 (-0.06 to 0.25) days (P = 0.25) and 0.28 (-0.05 to 0.62) days (P = 0.2) in the intermediate and low oxygen groups, respectively. Low FiO2 was associated with increased surgical site infection: the adjusted odds ratio (OR) for low compared with high FiO2 was 1.53 (95% CI 1.12-2.10). Increasing FiO2 was associated with respiratory complications: the adjusted OR associated with each 10% point increase in FiO2 was 1.17 (95% CI 1.08-1.26) and the incidence of being admitted to an ICU had an adjusted OR of 1.1 (95% CI 1.03-1.18). Conclusions: We found potential benefits, and risks, associated with liberal intraoperative oxygen administration indicating that randomised controlled trials are warranted.

Perioperative oxygen administration in patients undergoing major non-cardiac surgery under general anaesthesia in Australia and New Zealand.

The practice of anaesthetists relating to the administration of intraoperative oxygen has not been previously quantified in Australia and New Zealand. The optimal regimen of intraoperative oxygen administration to patients undergoing surgery under general anaesthesia is not known, and international recommendations for oxygen therapy are contradictory; the World Health Organization (WHO) recommend administering an intraoperative fraction of inspired oxygen of at least 0.8, while the World Federation of Societies of Anaesthesiologists, British Thoracic Society, and Thoracic Society of Australia and New Zealand recommend a more restrictive approach. We conducted a prospective observational study to describe the pattern of intraoperative oxygen administration among anaesthetists in Australia and New Zealand and, second, to determine the proportion of anaesthetists who administer intraoperative inspired oxygen in accordance with the WHO recommendations. We identified 150 anaesthetists from ten metropolitan hospitals in Australia and New Zealand and observed the patterns of intraoperative oxygen administration to American Society of Anesthesiologists physical status classification (ASA) 3 or 4 patients undergoing prolonged surgery under general anaesthesia. The median (interquartile range) intraoperative time-weighted mean fraction of inspired oxygen (FiO2) for all participants in the study was 0.47 (0.40-0.55). Three out of 150 anaesthetists (2%, 95% confidence interval 0.4 to 5.7) administered an average intraoperative FiO2 of at least 0.8. These findings indicate that most anaesthetists routinely administer an intermediate level of oxygen for ASA 3 or 4 adult patients undergoing prolonged surgery in Australia and New Zealand, rather than down-titrating inspired oxygen to a target pulse oximetry reading (SpO2) or administering liberal perioperative oxygen therapy in line with the current WHO recommendation.

A survey of self-reported use of cricoid pressure amongst Australian and New Zealand anaesthetists: Attitudes and practice.

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.