Therapeutic Suggestions During General Anesthesia Reduce Postoperative Nausea and Vomiting in High-Risk Patients - A Post hoc Analysis of a Randomized Controlled Trial.

Postoperative nausea and vomiting (PONV) are one of the most adverse events after general anesthesia, a distressing experience, and pose a risk to the patient. Despite advances in drug prophylaxis and PONV treatment, the incidence remains high and additional non-pharmacological treatments are needed. In this post hoc analysis of a recently published double-blind multicenter randomized controlled trial on the efficacy of intraoperative therapeutic suggestions on postoperative opioid dosage, we analyzed the effects of intraoperative therapeutic suggestions on PONV. We focus on patients with a high risk of PONV (Apfel risk score of 3-4) and distinguished early (first two postoperative hours) and delayed PONV (2-24 h). A total of 385 patients with a moderate or high risk for PONV were included. The incidence of early and delayed PONV was reduced (22.7-18.3 and 29.9-24.1%, respectively), without statistical significance, whereas in high-risk patients (n = 180) their incidence was nearly halved, 17.2 vs. 31.2% (p = 0.030) and 20.7 vs. 34.4% (p = 0.040), corresponding to a number needed to treat of 7 to avoid PONV. In addition, there was a significant reduction in PONV severity. In a multivariate logistic regression model, assignment to the control group (OR 2.2; 95% CI: 1.1-4.8) was identified as an independent predictor of the occurrence of early PONV. Our results indicate that intraoperative therapeutic suggestions can significantly reduce the incidence of PONV in high-risk patients. This encourages the expansion of therapeutic suggestions under general anesthesia, which are inexpensive and virtually free of side effects. Clinical Trial Registration: German Clinical Trials Register, https://drks.de, registration number: DRKS00013800.

Effect of therapeutic suggestions during general anaesthesia on postoperative pain and opioid use: multicentre randomised controlled trial.

OBJECTIVE: To investigate the effect of therapeutic suggestions played to patients through earphones during surgery on postoperative pain and opioid use. DESIGN: Blinded randomised controlled study. SETTING: Five tertiary care hospitals in Germany. PARTICIPANTS: 385 of 400 patients consecutively recruited from January to December 2018 who were to undergo surgery for 1-3 hours under general anaesthesia. In the per protocol analysis 191 patients were included in the intervention group and 194 patients in the control group. INTERVENTION: The intervention comprised an audiotape of background music and positive suggestions based on hypnotherapeutic principles, which was played repeatedly for 20 minutes followed by 10 minutes of silence to patients through earphones during general anaesthesia. Patients in the control group were assigned to a blank tape. MAIN OUTCOME MEASURES: The main outcome was dose of opioid administered by patient controlled analgesia or nurse controlled analgesia within the first postoperative 24 hours, based on regular evaluation of pain intensity on a numerical rating scale (range 0-10, with higher scores representing more severe pain). RESULTS: Compared with the control group, the intervention group required a significantly (P=0.002) lower opioid dose within 24 hours after surgery, with a median of 4.0 mg (interquartile range 0-8) morphine equivalents versus 5.3 (2-12), and an effect size (Cohen's d) of 0.36 (95% confidence interval 0.16 to 0.56). The number of patients who needed opioids postoperatively was significantly (P=0.001) reduced in the intervention group: 121 of 191 (63%, 95% confidence interval 45% to 70%) patients in the intervention group versus 155 of 194 (80%, 74% to 85%) in the control group. The number needed to treat to avoid postoperative opioids was 6. Pain scores were consistently and significantly lower in the intervention group within 24 hours after surgery, with an average reduction of 25%. No adverse events were reported. CONCLUSIONS: Therapeutic suggestions played through earphones during general anaesthesia could provide a safe, feasible, inexpensive, and non-drug technique to reduce postoperative pain and opioid use, with the potential for more general use. Based on the finding of intraoperative perception by a considerable number of patients, surgeons and anaesthetists should be careful about background noise and conversations during surgery. TRIAL REGISTRATION: German Clinical Trial Register DRKS00013800.

Lipoteichoic acid induces delayed myocardial protection in isolated rat hearts: a comparison with endotoxin.

OBJECTIVE: Preconditioning with bacterial wall fragments lipopolysaccharide (LPS) or lipoteichoic acid (LTA) reduce myocardial infarct size after ischaemia and reperfusion (I/R) in rats. Preconditioning with LTA reduces neutrophil accumulation during reperfusion and thereby ameliorates one of myocardial reperfusion injury's most important mechanisms. In this study, we use an ex vivo model of regional myocardial I/R to investigate LTA versus LPS induced preconditioning in a system devoid of leukocytes. METHODS: Rats were subjected to LTA or LPS with or without dexamethasone pre-treatment. Twenty-four hours after LTA or LPS challenge, hearts were removed and retrogradely perfused in a Langendorff set-up. Hearts underwent 20 min of regional ischaemia followed by 2 h of reperfusion. Ischaemic preconditioning (IPC) was performed as a positive control. Myocardial infarct size was determined as the primary end-point. RESULTS: LTA and LPS preconditioning both lead to a marked reduction in infarct size similar to IPC, however, no significant differences were found between LTA and LPS. The reduction in infarct size was abrogated by dexamethasone pre-treatment. CONCLUSION: We conclude that preconditioning with LTA and likewise with LPS confers myocardial protection in an ex vivo setting devoid of leukocytes. Dexamethasone inhibits preconditioning, suggesting that the underlying mechanism is dependent upon induction of a systemic inflammatory response to a LTA or LPS stimulus.