Sex Differences in Cardiac and Cerebral Damage after Hypovolemic Cardiac Arrest

Resuscitation from haemorrhagic shock and the subsequent circulatory arrest remains a major clinical challenge in the care of trauma patients. Numerous experimental studies in sexually mature animals have shown a gender dimorphism in response to trauma and haemorrhagic shock. The first study was designed to evaluate sex differences in outcome after resuscitation from hypovolemic circulatory arrest. We intended to examine innate sex differences, and chose to study sexually immature animals. The study showed that cerebral cortical blood flow was greater, blood-brain-barrier was better preserved and neuronal injury was smaller in female as compared to male piglets. The second study demonstrated that female sex was associated with enhanced haemodynamic response, cardioprotection, and better survival. This cardioprotective effect was observed despite comparable estradiol and testosterone levels in male and female animals, indicating an innate gender-related cardioprotection. In both studies (I and II) female sex was associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (iNOS and nNOS). Thus in the study III we tested the hypothesis that exogenously administered 17β-estradiol (E2) could improve neurological outcome by NOS modulation. The results showed that compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption and a mitigated neuronal injury. There was also a significant correlation between nNOS and iNOS levels and neuronal injury. A hypothesis if female-specific cardioprotection may be attributed to a smaller NOS activity was tested in study IV. The animals received methylene blue (MB) during CPR, but were otherwise treated according to the same protocol as studies I-II. The female-specific cardioprotection could be attributed to a smaller NOS activity, but NOS inhibition with MB did not improve survival or myocardial injury, although it abated the difference between the sexes

Patient satisfaction with continuous epidural analgesia after major surgical procedures at a Swedish University hospital

Objective The use of epidural analgesia after major surgery is a well-established analgesia method. Epidural analgesia for postoperative pain relief needs to be monitored regularly in order to evaluate patient satisfaction and avoid side effects. However, due to the new available regional techniques, the role of epidural analgesia is being questioned and data about patient satisfaction is lacking. The current study was designed to evaluate patient satisfaction with epidural analgesia, its efficacy and reasons for premature termination of epidural analgesia. Materials and methods We conducted a retrospective survey of all patients who undergone surgery at Uppsala University hospital between October 2012 and January 2014 requiring continuous epidural analgesia for postoperative pain relief. Patients' satisfaction with epidural analgesia and its effectiveness were evaluated by using paper questionnaire. Results During the study period 579 epidurals were inserted in patients scheduled for vascular, hepatobiliary, esophageal and other major abdominal surgery. The average treatment time was 3.8 +/- 1.8 days. Epidural analgesia consisted either of bupivacaine 0.1%+sufentanil 1 mu g/ml solution or ropivacaine 0.2% solution. If patient needed opiates during treatment with epidural analgesia, only ropivacaine 0,2% solution was used. 494 (87.9%) patients were satisfied with their analgesia with no difference in satisfaction between sexes being observed. In 62 cases (11.2%) patient controlled analgesia was used on top of epidural analgesia with ropivacaine 0.2% solution, and 50.8% of patients were satisfied in this group. 514 (91.4%) patients were reported as having a good effect, 24 (4.3%) patients reported or were tested to show some effect, and 24 (4.3%) had no effect. No major neurological complications (epidural hematoma or abscess) were observed. Conclusions Our retrospective survey indicates that patients are satisfied with continuous epidural analgesia used in major surgery

The Impact on Postoperative Outcomes of Intraoperative Fluid Management Strategies During Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background  The impact of intraoperative fluid management during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on postoperative outcomes has been poorly investigated. This study aimed to investigate the impact of intraoperative fluid management strategy on postoperative outcomes and survival focusing on postoperative hemorrhage.   Methods  509 patients undergoing CRS and HIPEC at Uppsala University Hospital/Sweden 2004-2017 were categorized into two groups according to the intraoperative fluid management strategy: pre-goal directed therapy (pre-GDT) and goal directed therapy (GDT), where a hemodynamic monitor (CardioQ or FloTrac/Vigileo) was used to optimize fluids management. Impact on morbidity, postoperative hemorrhage, length-of-stay and survival was analyzed.  Results The pre-GDT group received higher intraoperative fluid volume compared to the GDT group (mean 19.9 vs. 16.2 ml/kg/h, p<0.001). Overall postoperative morbidity Grade III-V was higher in the GDT group (30% vs. 22%, p=0.03). Multivariable adjusted odds ratio (OR) for Grade III-V morbidity was 1.80 (95%CI 1.10-3.10, p=0.02) in the GDT group. Numerically, more cases of postoperative hemorrhage were found in the GDT group (9% vs. 5%, p=0.09), but no correlation was observed in the multivariable analysis 1.37 (95%CI 0.64-2.95, p=0.40). An oxaliplatin regimen was a significant risk factor for postoperative hemorrhage (p=0.03). Mean length of stay was shorter in the GDT group (17 vs. 26 days, p<0.0001). Survival did not differ between the groups. Conclusion While GDT management increased the risk for postoperative morbidity, it was associated with shortened hospital stay. Intraoperative fluid management during CRS and HIPEC did not affect the postoperative risk for hemorrhage, while the use of an oxaliplatin regimen did.

Plasma cytokine levels in spinal surgery with sevoflurane or total intravenous propofol anesthesia : A post hoc analysis of a randomized controlled trial

Surgical tissue trauma stimulates an inflammatory response resulting in increased levels of cytokines which could contribute to acute kidney injury (AKI). It is not clear if anesthetic modality affects this response. We aimed to investigate the role of anesthesia in a healthy surgical population on the inflammatory response and the correlation to plasma creatinine. This study is a post hoc analysis of a published randomized clinical trial. We analyzed plasma from patients who underwent elective spinal surgery randomized to either total intravenous propofol anesthesia (n = 12) or sevoflurane anesthesia (n = 10). The plasma samples were collected before anesthesia, during anesthesia, and 1 h after surgery. Plasma cytokine levels after surgery were analyzed for correlations with duration of surgical insult and change in plasma creatinine concentration. The cytokine interleukin-6 (IL-6) was increased after surgery compared with preoperatively. IL-6 was higher in the sevoflurane group than the propofol group after surgery. No patient developed AKI, but plasma creatinine was increased postoperatively in the sevoflurane group. There was a significant association between surgical time and plasma IL-6 postoperatively. No significant correlation between change in plasma creatinine and IL-6 was detected. The cytokines IL-4, IL-13, Eotaxin, Interferon γ-Induced Protein 10 (IP-10), Granulocyte Colony-Stimulating Factor (G-CSF), Macrophage Inflammatory Protein-1β (MIP-1β), and Monocyte Chemoattractant Protein 1 (MCP-1) were lower postoperatively than before surgery independent of anesthetic modality. This post hoc analysis revealed that plasma IL-6 was increased after surgery and more so in the sevoflurane group than the propofol group. Postoperative plasma IL-6 concentration was associated with surgical time

Analgesic effects of dexmedetomidine and remifentanil on periprocedural pain during percutaneous ablation of renal carcinoma

Background: Percutaneous ablation of renal carcinoma is frequently a favourable treatment alternative, especially in elderly patients suffering from co-morbidities. Also, it is less resource-demanding than conventional surgery of renal carcinoma, and one may, therefore, assume that the incidence of this procedure may increase. Analgesia is necessary during this intervention. The aim of this study was to explore the possibility of analgosedation and its relation to patient comfort and safety during percutaneous ablation of renal carcinoma. Methods: Forty-six patients, sedated with dexmedetomidine and remifentanil, supplemented with infiltration anaesthesia (lidocaine 1%), underwent percutaneous (radiofrequency or microwave) ablation of renal carcinoma in this prospective study. Results: The patients expected pain intensity around the numerical rating score (NRS) 4.5 (interquartile range [IQR] 3.5–5.5), which was slightly lower than pain experienced during the procedure NRS 5 (IQR 2–7; p = 0.49). Eight percent of the patients needed supplementary morphine during the ablation procedure. Sedation score did not differ during ablation, at arrival to or discharge from the recovery ward. Median periprocedural treatment time was 12 minutes (IQR 12–16). Treatment time did not correlate with experienced pain (R2=0.000074, p = 0.96). The median length of stay in the recovery room was 120 minutes (IQR 84–154). There were seven serious adverse events. Conclusions: This proof-of-concept study has shown that analgosedation during percutaneous ablation of renal carcinoma can be performed with a generally tolerable degree of patient satisfaction. However, pain occurs and should be managed adequately. Patient safety must be a major concern for the anaesthetic care

Renal function during sevoflurane or total intravenous propofol anaesthesia a single-centre parallel randomised controlled study.

BACKGROUND: The choice of anaesthetic may influence regulation of renal perfusion and function. We investigated renal function in patients anaesthetised with propofol or sevoflurane before surgery and postoperatively. METHODS: Patients with ASA physical status 1-2 planned for spinal surgery were randomised to propofol or sevoflurane anaesthesia. Blood and urine were collected before anaesthesia, during anaesthesia (before surgery), during postoperative care, and the day after surgery. RESULTS: Twenty-seven patients completed the study protocol (average age, 51 yr; average BMI, 28 kg m-2) and 11 were women. Urine output and sodium excretion were lower during sevoflurane anaesthesia (n=14) than during propofol anaesthesia (n=13) (0.3 vs 1.1 ml kg-1 h-1 [P=0.01] and 2.6 vs 6.0 mmol h-1 [P=0.04], respectively). Urinary potassium excretion was lower during anaesthesia than after, without intergroup difference (2.3 vs 5.7 mmol h-1, P<0.001). Sevoflurane anaesthesia increased plasma renin compared with baseline (138 vs 23 mIU L-1, P<0.001) and propofol anaesthesia (138 vs 27 mIU L-1, P=0.008). Plasma arginine-vasopressin did not change significantly during anaesthesia, but was elevated postoperatively compared with baseline irrespective of anaesthetic (21 vs 12 ng L-1, P=0.02). Sevoflurane caused higher postoperative plasma creatinine than propofol (83 vs 66 mmol L-1, P=0.01). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not change significantly in either group. CONCLUSIONS: Sevoflurane anaesthesia reduced urine output and sodium excretion and increased plasma renin compared with propofol anaesthesia. The impact of this on acute kidney injury and fluid resuscitation during surgery warrants further investigation. CLINICAL TRIAL REGISTRATION: EudraCT: 2017-001646-10; Clinicaltrials.gov: NCT0333680

Severe pulmonary complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are common and contribute to decreased overall survival.

BACKGROUND AND OBJECTIVES: Extensive abdominal surgery is associated with the risk of postoperative pulmonary complications. This study aims to explore the incidence and risk factors for developing postoperative pulmonary complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and to analyze how these complications affect overall survival. METHODS: Data were collected on 417 patients undergoing surgery between 2007 and2017 at Uppsala University Hospital, Sweden. Postoperative pulmonary complications were graded according to the Clavien-Dindo classification system where Grade ≥ 3 was considered a severe complication. A logistic regression analysis was used to analyze risk factors for postoperative pulmonary complications and a Cox proportional hazards model to assess impact on survival. RESULTS: Seventy-two patients (17%) developed severe postoperative pulmonary complications. Risk factors were full thickness diaphragmatic injury and/or diaphragmatic resection [OR 5.393, 95% CI 2.924-9.948, p = < 0.001]. Severe postoperative pulmonary complications, in combination with non-pulmonary complications, contributed to decreased overall survival [HR 2.285, 95% CI 1.232-4.241, p = 0.009]. CONCLUSIONS: Severe postoperative pulmonary complications were common and contributed to decreased overall survival. Full thickness diaphragmatic injury and/or diaphragmatic resection were the main risk factors. This finding emphasizes the need for further research on the mechanisms behind pulmonary complications and their association with mortality

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI –5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications