Is there a role for ketones as alternative fuel in critical illness?

PURPOSE OF REVIEW: The evidence base advocating ketones as an alternative substrate for critically ill patients is expanding. We discuss the rationale for investigating alternatives to the traditional metabolic substrates (glucose, fatty acids and amino acids), consider evidence relating to ketone-based nutrition in a variety of contexts, and suggest the necessary future steps. RECENT FINDINGS: Hypoxia and inflammation inhibit pyruvate dehydrogenase, diverting glucose to lactate production. Skeletal muscle beta-oxidation activity falls, decreasing acetyl-CoA generation from fatty acids and subsequent ATP generation reduction.The benefits of induced ketosis are well established in epilepsy, whilst the evidence base for ketogenic diet therapy in other neurological pathology, such as traumatic brain injury and neurodegenerative diseases, is expanding. Evidence of upregulation of ketone metabolism in the hypertrophied and failing heart suggests that ketones may be utilized as an alternative fuel source to sustain myocardial function. Ketogenic diets stabilize immune cell homeostasis, promote cell survival following bacterial infection and inhibit the NLRP3 inflammasome, preventing the release of pro-inflammatory cytokines - interleukin (IL)-1ß and IL-18. SUMMARY: Whilst ketones provide an attractive nutritional option, further research is required to determine whether the proposed benefits are translatable to critically unwell patients.

Efficacy of local anaesthetic infiltration via wound catheters after open hepatic surgery: a systematic review and meta-analysis.

BACKGROUND: This study analysed whether local anaesthetic wound catheter infiltration (LA-WCI) as an adjunct to intravenous patient-controlled analgesia (IV-PCA) provides superior outcomes compared to IV-PCA alone following liver resection. METHODS: A systematic review and meta-analysis was conducted for randomised control trials (RCTs) comparing LA-WCI with IV-PCA(LA-WCI group) versus IV-PCA alone (IV-PCA group). PubMed and the Cochrane Library were searched for relevant articles. RESULTS: Six RCTs with a total of 440 patients were included. Opioid use in the initial 48 h was less in the LA-WCI group [MD -21.27 mg (-39.39,-3.15), p = 0.02]. Pain scores were lower in the LA-WCI group at rest at POD0 (post-operative day 0)6-8 h (p = 0.0009), POD1AM(p = 0.01), POD1PM(p = 0.02) and POD2 (p = 0.0006), and exertion at POD0 0-2 h (p = 0.05), POD1AM(p = 0.03), POD1PM(p = 0.03), POD2 (p = 0.03) and POD3 (p = 0.01). LA-WCI group had reduced length of hospital stay [MD -1.32 days (-2.23,-0.40),p = 0.005], time to ambulation [MD -5.94 h (-8.47,-3.42),p = 0.00001] and incidence of nausea and vomiting (PONV) [OR 0.17 (0.07,0.43),p = 0.0002]. No differences were observed in length of intensive care unit (ICU) stay or incidence of surgical site infections. DISCUSSION: LA-WCI as an adjunct to opiate IV-PCA post-hepatectomy reduces opioid use, pain scores at multiple time points at rest and exertion, length of hospital stay, time to ambulation and PONV. However, LA-WCI use does not alter length of ICU stay or incidence of wound infection.

Safety and efficacy of telephone clinics during the COVID-19 pandemic in the provision of care for patients with cancer.

BACKGROUND: Due to the COVID-19 pandemic, telephone clinics have been utilised to reduce the risk of transmission. Evidence supporting its quality and safety is required. AIMS: Assess the efficacy and safety of telephone clinics in delivering care to established oncology patients and assess patient and health professionals' preference (telephone vs face-to-face clinics). METHODS: Retrospective chart audit in the month preceding and month following the introduction of telephone clinics at the Gold Coast University Hospital and a patient and health professional questionnaire. RESULTS: In total, 1212 clinical encounters occurred in the month post the introduction of telephone clinics (vs 1208 encounters prior). There were no statistically significant differences in 24-h (18 vs 22, P = 0.531) or 7-day admissions (50 vs 46, P = 0.665) comparing encounters in the month prior to the introduction of telephone clinics versus the month post, but there was a statistically significant difference in 30-day mortality post systemic therapy in favour of the post-telephone clinic period (7 vs 0 patients, P = 0.008). Of the 222 patients who undertook the questionnaire, 42.3% preferred telephone clinics (95% confidence interval (CI) 35.97-48.97), 25.2% preferred face-to-face clinics (95% CI 19.92-31.39) and 32.4% did not prefer one method over another. Of the 24 health professionals who undertook the questionnaire, 70.8% felt patients preferred phone clinics. CONCLUSIONS: Generally, patients and clinicians viewed telephone clinics favourably. Nevertheless, a large portion of patients still prefer face-to-face clinics. Services should be tailored to individual preferences. Although there were no 'red flags' in terms of mortality or admission rates, further longitudinal research is required.

Creatine supplementation for optimization of physical function in the patient at risk of functional disability: A systematic review and meta-analysis.

BACKGROUND: The efficacy of creatine replacement through supplementation for the optimization of physical function in the population at risk of functional disability is unclear. METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane Library, and CINAHL from inception to November 2022. Studies included were randomized controlled trials (RCTs) comparing creatine supplementation with placebos in older adults and adults with chronic disease. The primary outcome was physical function measured by the sit-to-stand test after pooling data using random-effects modeling. We also performed a Bayesian meta-analysis to describe the treatment effect in probability terms. Secondary outcomes included other measures of physical function, muscle function, and body composition. The risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: We identified 33 RCTs, comprising 1076 participants. From six trials reporting the primary outcome, the pooled standardized mean difference (SMD) was 0.51 (95% confidence interval [CI]: 0.01-1.00; I2 = 62%; P = 0.04); using weakly informative priors, the posterior probability that creatine supplementation improves physical function was 66.7%. Upper-body muscle strength (SMD: 0.25; 95% CI: 0.06-0.44; I2 = 0%; P = 0.01), handgrip strength (SMD 0.23; 95% CI: 0.01-0.45; I2 = 0%; P = 0.04), and lean tissue mass (MD 1.08 kg; 95% CI: 0.77-1.38; I2 = 26%; P < 0.01) improved with creatine supplementation. The quality of evidence for all outcomes was low or very low because of a high risk of bias. CONCLUSION: Creatine supplementation improves sit-to-stand performance, muscle function, and lean tissue mass. It is crucial to conduct high-quality prospective RCTs to confirm these hypotheses (PROSPERO number, CRD42023354929).

Laparoscopic Management of Acute Small Bowel Obstruction in Non-Selected Patients: A 10-Year Experience.

The laparoscopic approach to the management of small bowel obstruction (SBO) has been associated with reduced length of hospital stay, complications, and mortality. The laparoscopy-first approach has been limited to highly selective cases to date. In this retrospective observational study, we report our 10-year experience and outcomes within a dedicated Emergency Surgery unit that adopted a non-selective approach in the laparoscopic management of SBO. The surgical approach to all patients that underwent surgery for SBO by an experienced Emergency Surgeon, over a period of 10 years, was divided into two groups of open surgery (OS) or laparoscopy-first (LF). Outcomes included length of stay, complications, mortality, readmission rates and reasons for conversion. Data were reviewed to identify patterns of learning. A total of 189 patients were included in the study. A total of 81.5% were managed with an LF approach. Of these, 25.3% required conversion. LF patients had a similar length of stay, lower 30-day readmission rates and wound complications. Reasons for conversion included need for bowel resection, perforation, and malignancy. Our study had a high intention-to-treat LF population and identified major indications for conversion. As our laparoscopic experience increased, conversion rates substantially reduced. We propose that a LF approach is feasible and can benefit from training within dedicated Emergency Surgery teams.

ChAdOx1 nCoV-19 (AZD1222) vaccine candidate significantly reduces SARS-CoV-2 shedding in ferrets.

Vaccines against SARS-CoV-2 are likely to be critical in the management of the ongoing pandemic. A number of candidates are in Phase III human clinical trials, including ChAdOx1 nCoV-19 (AZD1222), a replication-deficient chimpanzee adenovirus-vectored vaccine candidate. In preclinical trials, the efficacy of ChAdOx1 nCoV-19 against SARS-CoV-2 challenge was evaluated in a ferret model of infection. Groups of ferrets received either prime-only or prime-boost administration of ChAdOx1 nCoV-19 via the intramuscular or intranasal route. All ChAdOx1 nCoV-19 administration combinations resulted in significant reductions in viral loads in nasal-wash and oral swab samples. No vaccine-associated adverse events were observed associated with the ChAdOx1 nCoV-19 candidate, with the data from this study suggesting it could be an effective and safe vaccine against COVID-19. Our study also indicates the potential for intranasal administration as a way to further improve the efficacy of this leading vaccine candidate.

'Red carding' for relatives.

My colleagues and I recently looked after a patient on our acute trauma ward. The patient was well looked after, however her daughter made life very difficult for the nurses - to the point where the head of nursing visited daily to appease her.