Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Muscular Tissue Oxygen Saturation and Posthysterectomy Nausea and Vomiting: The iMODIPONV Randomized Controlled Trial.

BACKGROUND: Suboptimal tissue perfusion and oxygenation during surgery may be responsible for postoperative nausea and vomiting in some patients. This trial tested the hypothesis that muscular tissue oxygen saturation-guided intraoperative care reduces postoperative nausea and vomiting. METHODS: This multicenter, pragmatic, patient- and assessor-blinded randomized controlled (1:1 ratio) trial was conducted from September 2018 to June 2019 at six teaching hospitals in four different cities in China. Nonsmoking women, 18 to 65 yr old, and having elective laparoscopic surgery involving hysterectomy (n = 800) were randomly assigned to receive either intraoperative muscular tissue oxygen saturation-guided care or usual care. The goal was to maintain muscular tissue oxygen saturation, measured at flank and on forearm, greater than baseline or 70%, whichever was higher. The primary outcome was 24-h postoperative nausea and vomiting. Secondary outcomes included nausea severity, quality of recovery, and 30-day morbidity and mortality. RESULTS: Of the 800 randomized patients (median age, 50 yr [range, 27 to 65]), 799 were assessed for the primary outcome. The below-goal muscular tissue oxygen saturation area under the curve was significantly smaller in patients receiving muscular tissue oxygen saturation-guided care (n = 400) than in those receiving usual care (n = 399; flank, 50 vs. 140% · min, P < 0.001; forearm, 53 vs. 245% · min, P < 0.001). The incidences of 24-h postoperative nausea and vomiting were 32% (127 of 400) in the muscular tissue oxygen saturation-guided care group and 36% (142 of 399) in the usual care group, which were not significantly different (risk ratio, 0.89; 95% CI, 0.73 to 1.08; P = 0.251). There were no significant between-group differences for secondary outcomes. No harm was observed throughout the study. CONCLUSIONS: In a relatively young and healthy female patient population, personalized, goal-directed, muscular tissue oxygen saturation-guided intraoperative care is effective in treating decreased muscular tissue oxygen saturation but does not reduce the incidence of 24-h posthysterectomy nausea and vomiting.

Efficacy of amisulpride on postoperative nausea and vomiting: a systematic review and meta-analysis.

AIM AND BACKGROUND: Postoperative nausea and vomiting (PONV) remains a significant clinical problem for surgical patients. Amisulpride is a well-studied D2/D3 antagonist that has the potential to be used for preventing and treating PONV. Our aim was to assess the efficacy and safety of amisulpride for prevention and treatment of PONV through a systematic review and meta-analysis. METHOD: A systematic literature search was performed using MEDLINE, EMBASE, PUBMED, clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials from their inception to Feb 15th, 2019. The efficacy outcome was the incidence of complete response, defined as no emesis and no rescue antiemetic use in a 24-h period after study drug administration. The safety outcomes were the adverse effects associated with amisulpride. RESULTS: Five studies comprising 3243 patients met inclusion critieria. Compared with placebo, amisulpride showed a significantly improved incidence of complete response [relative risk (RR): 1.30; 95% confidence interval (CI): 1.20-1.41; P < 0.00001, I2 = 0%] with firm evidence from the trial sequential analysis. Particularly, the amisulpride at 5 mg dose indicated a significant benefit than placebo [relative risk (RR): 1.28; 95% confidence interval (CI): 1.18-1.39; P < 0.00001, I2 = 4%]. The adverse event profile of amisulpride was generally similar to the placebo. CONCLUSION: Based on our findings, low-dose, intravenous amisulpride is safe and efficacious for the prevention and treatment of PONV compared to placebo. Further studies are needed to explore the optimal dose and timing. CLINICAL TRIAL REGISTRATION: PROSPERO: CRD42019121483.

The Roles of Chemokine CXCL13 in the Development of Bone Cancer Pain and the Regulation of Morphine Analgesia in Rats.

Chemokines are important regulators of immune, inflammatory, and neuronal responses in peripheral and central pain pathway. The aim of this study was to investigate whether chemokine (C-X-C motif) ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) involve in the development of bone cancer pain (BCP) and the regulation of morphine analgesia in rats. The change of pain behaviors in BCP rats were measured by testing paw withdrawal threshold (PWT). The levels of CXCL13, CXCR5 and signal pathway proteins (p-p38, p-ERK and p-AKT etc.) in the spinal cord were measured via western blots. The expression of CXCL13 and CXCR5 in spinal cord was increased in BCP rats. The BCP rats showed decrease of PWTs, which was relieved by CXCR5i. Intrathecally injection of murine recombinant CXCL13 (mrCXCL13) decreased the PWTs of BCP rats and opposed morphine-induced analgesia in BCP rats. In BCP rats, the signal pathway proteins (p38, ERK and AKT) in the spinal cord were activated. CXCL13 and morphine had contrary effect on the phosphorylation of these proteins. MrCXCL13 directly increased the levels of p-p38, p-ERK and p-AKT in BCP rats. However, morphine decreased the levels of these proteins in BCP rats. While blocking the activation of p-p38, p-ERK and p-AKT, morphine analgesia was enhanced. These results suggest CXCL13 participated in bone cancer pain and opposed morphine analgesia via p38, ERK and AKT pathways. It may be a target to enhance pain management in cancer pain patients.

Efficacy of Internet-delivered cognitive-behavioral therapy for the management of chronic pain in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Pediatric chronic pain is relatively common in the world. Although cognitive behavior therapy (CBT) has been shown to be efficacious in children and adolescents, it is generally recognized that availability and accessibility of CBT are limited. While Internet-delivered cognitive-behavioral therapy (ICBT) performs better in these areas. OBJECTIVES: This systematic review aims to evaluate the clinical effects of ICBT for chronic pain in youth when compared with the control treatments. METHODS: We searched electronic databases to identify randomized controlled trials that compared ICBT with the control therapy for pediatric chronic pain. The primary outcomes were 95% confidence intervals and mean difference or standardized mean difference in change of pain intensity and activity limitations. RESULTS: Four trials met the inclusion criteria with a total of 404 participants of whom 208 received ICBT. Compared with pretreatment, children reported significant, medium to large benefits on pain intensity, activity limitations, and parental protective behaviors after receiving ICBT immediately. Significant small to medium effects were found for outcomes of depressive symptoms, anxiety, and sleep quality from baseline to post-treatment in the ICBT group. But most measures of ICBT did not show statistically significant superiority to those of the control conditions, except parental protective behaviors. Generally children and their parents were highly acceptable and satisfied with ICBT. CONCLUSION: ICBT for physical and psychological conditions in youth with chronic pain is a full potential therapy; it can be successful on clinically effects and socioeconomic benefits. However, only limited data supported the conclusion, we require further methodologically robust trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017069811.

Impact of inhalational versus intravenous anaesthesia on early delirium and long-term survival in elderly patients after cancer surgery: study protocol of a multicentre, open-label, and randomised controlled trial.

INTRODUCTION: Elderly patients who have solid organ cancer often receive surgery. Some of them may develop delirium after surgery and delirium development is associated with worse outcomes. Furthermore, despite all of the advances in medical care, the long-term survival in cancer patients is far from optimal. Evidences suggest that choice of anaesthetics during surgery, that is, either inhalational or intravenous anaesthetics, may influence outcomes. However, the impact of general anaesthesia type on the occurrence of postoperative delirium is inconclusive. Although retrospective studies suggest that propofol-based intravenous anaesthesia was associated with longer survival after cancer surgery when compared with inhalational anaesthesia, prospective studies as such are still lacking. The purposes of this randomised controlled trial are to test the hypotheses that when compared with sevoflurane-based inhalational anaesthesia, propofol-based intravenous anaesthesia may reduce the incidence of early delirium and prolong long-term survival in elderly patients after major cancer surgery. METHODS AND ANALYSIS: This is a multicentre, open-label, randomised controlled trial with two parallel arms. 1200 elderly patients (≥65 years but <90 years) who are scheduled to undergo major cancer surgery (with predicted duration ≥2 hours) are randomised to receive either sevoflurane-based inhalational anaesthesia or propofol-based intravenous anaesthesia. Other anaesthetics and supplemental drugs including sedatives, opioids and muscle relaxants are administered in both arms according to routine practice. The primary early outcome is the incidence of 7-day delirium after surgery and the primary long-term outcome is the duration of 3-year survival after surgery. ETHICS AND DISSEMINATION: The study protocol has been approved by the Clinical Research Ethics Committees of Peking University First Hospital (2015[869]) and all participating centres. The results of early and long-term outcomes will be analysed and reported separately. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-15006209; NCT02662257; NCT02660411.

Influence of laparoscopic carbon dioxide pneumoperitoneum on neonate circulation and respiration.

OBJECTIVE: This study investigated the influence of laparoscopic carbon dioxide (CO2) pneumoperitoneum on neonate circulation and respiration. METHODS: The study included neonates undergoing elective laparoscopic abdominal surgery. CO2 insufflation pressure was maintained within 8-14 mmHg for pneumoperitoneum creation. Heart rate (HR), mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), partial pressure of end-tidal carbon dioxide (P ETCO2) and maximum inspiratory pressure were monitored continuously. Arterial blood samples were collected: 5 min before pneumoperitoneum creation (baseline); 5, 10, and 20 min after CO2 insufflation; 10 min after CO2 exsufflation; 10 min after surgery. pH, partial pressure of CO2 (PaCO2) and arterial oxygen saturation (SaO2) were also measured. RESULTS: Thirty-six neonates were included. HR and MAP significantly increased after pneumoperitoneum creation, then decreased to baseline after CO2 exsufflation. PaCO2 and P ETCO2 were significantly higher after pneumoperitoneum creation, whereas pH was significantly lower 20 min after pneumoperitoneum creation compared with baseline. No significant differences were observed in SpO2 and SaO2. CONCLUSION: CO2 pneumoperitoneum had a significant effect on neonatal circulation and respiration, suggesting that the pneumoperitoneal pressure should be limited within a certain range in neonates undergoing laparoscopic surgery.

Hydrogen sulfide attenuates surgical trauma-induced inflammatory response and cognitive deficits in mice.

BACKGROUND: It has been increasingly reported that peripheral surgical trauma triggers neuroinflammatory processes associated with postoperative cognitive dysfunction, and that mitigating the neuroinflammatory effects of surgery prevents surgery-induced cognitive dysfunction. Endogenously produced hydrogen sulfide (H2S) has multiple functions in the brain, and an increasing number of studies have demonstrated its anti-inflammatory effects. The present study was designed to investigate the effects of sodium hydrosulfide (NaHS), an H2S donor, on the cognitive impairment of mice as they experience neuroinflammatory changes induced by surgery. METHODS: Each mouse received 5 mg/kg NaHS or volume-matched vehicle administration by intraperitoneal injection once daily, 3 d before surgery, on the day of surgery, and for 3 d afterward. We assessed cognitive function using a Morris water maze and evaluated expression of proinflammatory cytokines tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in the serum and hippocampus. We performed each test 1, 3, and 7 d after surgery. RESULTS: Hippocampal-dependent memory impairment in mice after surgery was associated with increased serum proinflammatory cytokines, as well as proinflammatory cytokine expression in the hippocampus. Presurgery treatment with NaHS, an H2S donor, significantly attenuated surgery-induced memory impairment and expression of proinflammatory cytokines in the serum and hippocampus. CONCLUSIONS: These findings suggest that intraperitoneal injections of NaHS could significantly mitigate surgery-induced memory impairment in mice, which is strongly associated with reduced levels of serum and hippocampal proinflammatory cytokines.