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-1ß (MIP-1ß), 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.

Spinal drain-related complications after complex endovascular aortic repair using a prophylactic automated volume-directed drainage protocol.

OBJECTIVE: A common measure to lower the risk for spinal cord ischemia (SCI) during complex endovascular aortic repair (cEVAR) is prophylactic cerebrospinal fluid drainage (CSFD). This method has caused controversy because of drain-related complications. Spinal drains are usually pressure directed. The objective of this study was to evaluate the risk of CSFD-related complications and SCI within the context of an automated volume-directed drain protocol. METHODS: This is a retrospective, single-center study of all cEVARs with CSFD at a tertiary vascular center between January 2014 and December 2020. Demographics, complications, and spinal drain data were recorded. All drainages were volume based using an automatic drainage system (LiquoGuard7; Möller Medical GmbH). Spinal drain complications were categorized as disabling and nondisabling according to the modified Rankin scale. The primary end point was any CSFD-related complication. RESULTS: A total of 448 cEVAR patients were identified, of whom 147 (32.8%) had prophylactic CSFD. The mean age was 69 years (63% male). The most common pathology (61%) was thoracoabdominal aortic aneurysm, and the most common procedure was branched EVAR (55.1%). Eighteen (12.2%) patients developed a CSFD-related complication, whereof three (2%) were disabling. Nineteen (13%) patients developed SCI: 12 (8.4%) paraparetic, 5 (3.4%) paraplegic, and 2 (1.4%) paresthesias. Of these, 13 (68%) had full reversal of symptoms, whereas 6 patients (4%) had residual symptoms and were deemed disabling. Drain-related complications were more common in patients with SCI (31.6%) compared with those without (9.4%, P = .014). In the latter group, only two patients (1.6%) developed a disabling drain-related complication. CONCLUSIONS: Selective use of prophylactic, automated volume-directed CSFD in patients at high risk for SCI was associated with a high incidence of complications and should be used with caution. Among those developing SCI, reversal was achieved frequently with increased CSFD volume, but at the price of more bleeding complications.

Surgical Outcome Risk Tool (SORT) to predict 30-day postoperative mortality in a mixed surgical population in Swedish tertiary hospitals.

BACKGROUND: The Surgical Outcome Risk Tool (SORT) was derived and validated in the UK to improve preoperative prediction of postoperative risk. The aim of this study was to validate the SORT in a European mixed-case surgical population outside of the UK. METHODS: The study included patients aged at least 18 years with ASA Physical Status (ASA-PS) grades I-V who underwent non-cardiac surgery at four tertiary hospitals in Sweden between November 2015 and February 2016. Exclusion criteria were surgery under local anaesthesia and missing data on the SORT predictors (ASA-PS, surgical urgency, high-risk surgery, surgical severity, malignancy, age over 65 years). The outcome was 30-day mortality. Discrimination and calibration of the SORT were assessed using area under the receiver operating curve (AUROC) statistics and calibration plots. A sensitivity analysis was done in a high-risk subgroup (ASA-PS III or higher; surgical complexity major to Xmajor according to the SORT; gastrointestinal, orthopaedic, urogenital/obstetric surgery; and age at least 18 years). RESULTS: The validation cohort included 17 965 patients; median age was 58 (i.q.r. 40-70) years, 43.2 per cent were men, and the mortality rate at 30 days was 1.6 per cent. The SORT had excellent discrimination, with an AUROC of 0.91 (95 per cent c.i. 0.89 to 0.92), and good calibration. The high-risk subgroup (1807 patients) had a 30-day mortality rate of 5.6 per cent; in the sensitivity analysis, the SORT had good discrimination, with an AUROC of 0.79 (0.74 to 0.83), and calibration remained good. CONCLUSION: The estimates of the original the SORT for prediction of 30-day mortality were valid and reliable in a mixed-case surgical population in a non-UK European setting.

Point of Care Analysis of Hematology in the Operating Theater - a Prospective Observational Study of Accuracy and Feasibility.

BACKGROUND: Major surgery entails the risk of severe hemorrhage, and an optimized substitution with red blood cell (RBC) and platelet (PLT) transfusions necessitate rapid test results for RBCs/hemoglobin (HGB)/hematocrit (HCT), and PLTs. The HemoScreen (PixCell Medical, Yokneam Ilit, Israel) is an automated point-of-care hematology analyzer employing image analysis and single-use cuvettes. This study aimed to investigate the correspondence between the HemoScreen and standard laboratory testing (SLT) using the Sysmex XN-9000 in patients undergoing major surgery and to evaluate the feasibility in the operating theater. METHODS: A total of 145 blood samples from 91 adult patients were sampled during abdominal and orthopedic surgery and analyzed on both cell counters. Coefficient of variation (CV) was calculated, Passing-Bablok regression analysis was performed, and Bland-Altman plots were constructed. User experience was assessed through a questionnaire. RESULTS: The HemoScreen showed imprecision with a CV below 5%. Passing-Bablok regression showed positive proportional and negative constant errors for HGB and HCT, a positive proportional error for PLTs, but no dif-ference for RBCs. Bias in the Bland-Altman plots with limits of agreement: RBCs 0.09 x 1012/L (+/- 0.20 x 1012/L), HGB 1.1 g/L (+/- 8.4 g/L), HCT 0.4 % (+/- 2.6%), and PLTs 28.8 x 109/L (+/- 33 x 109/L). The analyzer was scored easy to use with shorter turnaround times compared to SLT. CONCLUSIONS: The HemoScreen is feasible and provides rapid test results with acceptable accuracy for the evaluated application but the two methods cannot be regarded as interchangeable based on the results in this study.

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.

ASA classification and surgical severity grading used to identify a high-risk population, a multicenter prospective cohort study in Swedish tertiary hospitals.

BACKGROUND: Identification of surgical populations at high risk for negative outcomes is needed for clinical and research purposes. We hypothesized that combining two classification systems, ASA (American Society of Anesthesiology physical status) and surgical severity, we could identify a high-risk population before surgery. We aimed to describe postoperative outcomes in a population selected by these two classifications system. METHODS: Data were collected in a Swedish multicentre, time-interrupted prospective, consecutive cohort study. Eligibility criteria were age ≥18 years, ASA ≥3, elective or emergent, major to Xmajor/complex (Specialist Procedure Codes used in United Kingdom), gastrointestinal, urogenital or orthopaedic procedures. Postoperative morbidity was identified by the Postoperative Morbidity Survey on postoperative days 3 ± 1, 7 ± 1, 10 + 5 and graded for severity by the Clavien-Dindo system. Mortality was assessed at 30, 180 and 360 days. RESULTS: Postoperative morbidity was 78/48/47 per cent on postoperative days 3/7/10. Majority of morbidities (67.5 per cent) were graded as >1 by Clavien-Dindo. Any type of postoperative morbidity graded >1 was associated with increased risk for death up to one year. The mortality was 5.7 per cent (61/1063) at 30 days, 13.3 per cent (142/1063) at 6 months and 19.1 per cent (160/1063) at 12 months. CONCLUSION: Severity classification as major to Xmajor/complex and ASA ≥3 could be used to identify a high-risk surgical population concerning postoperative morbidity and mortality before surgery. Combining the two systems future electronic data extraction is possible of a high-risk population in tertiary hospitals.

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 µg/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.

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.

Resuscitation with amiodarone increases survival after hemorrhage and ventricular fibrillation in pigs.

UNLABELLED: Supplemental digital content is available in the text. BACKGROUND: The aim of this experimental study was to compare survival and hemodynamic effects of a low-dose amiodarone and vasopressin compared with vasopressin in hypovolemic cardiac arrest model in piglets. METHODS: Eighteen anesthetized male piglets (with a weight of 25.3 [1.8] kg) were bled approximately 30% of the total blood volume via the femoral artery to a mean arterial blood pressure of 35 mm Hg in a 15-minute period. Afterward, the piglets were subjected to 4 minutes of untreated ventricular fibrillation followed by 11 minutes of open-chest cardiopulmonary resuscitation. At 5 minutes, circulatory arrest amiodarone 1 mg/kg was intravenously administered in the amiodarone group (n = 9), while the control group received the same amount of saline (n = 9). At the same time, all piglets received vasopressin 0.4 U/kg intravenously administered and hypertonic-hyperoncotic solution 3-mL/kg infusion for 20 minutes. Internal defibrillation was attempted from 7 minutes of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 hours after resuscitation. RESULTS: Three-hour survival was greater in the amiodarone group (p = 0.02). After the successful resuscitation, the amiodarone group piglets had significantly lower heart rate as well as greater systolic, diastolic, and mean arterial pressure. Troponin I plasma concentrations were lower and urine output was greater in the amiodarone group. CONCLUSION: Combined resuscitation with amiodarone and vasopressin after hemorrhagic circulatory arrest resulted in greater 3-hour survival, better preserved hemodynamic parameters, and smaller myocardial injury compared with resuscitation with vasopressin only.

Central nervous tissue damage after hypoxia and reperfusion in conjunction with cardiac arrest and cardiopulmonary resuscitation: mechanisms of action and possibilities for mitigation.

Only approximately 10% of patients encountering a cardiac arrest (CA) and subsequent cardiopulmonary resuscitation survive to a meaningful life. One of the most important causes for this low survival rate is the ischemia-reperfusion injury that hits the brain. This review summarizes some of the more important mechanisms causing cerebral injury. Thus, we describe some of our findings when performing genome-wide transcriptional profiling as well as histological and immunohistological staining of cerebral cortical areas. In order to shed some light on therapeutic opportunities, our findings relating to the use of induced mild hypothermia and methylene blue as neuroprotective agents are reviewed. Furthermore, we would like to share some interesting data on gender differences and effects of estrogen on the ensuing cerebral injury occurring after hypovolemic CA.

Modulation of nitric oxide expression with methylene blue does not improve outcome after hypovolemic cardiac arrest.

AIM OF THE STUDY: We recently reported that female sex protects against cerebral and cardiac injury after hypovolemic cardiac arrest (CA), independent of sex hormone effects. As female sex was also associated with a smaller increase in inducible and neuronal nitric oxide synthase (NOS), we hypothesised that nitric oxide inhibition with methylene blue (MB) improves the outcome, primarily in male animals. METHODS: Twenty sexually immature piglets (10 males and 10 females) were bled to mean arterial blood pressure of 35mmHg, and were subjected to 2 min of untreated CA followed by 8 min of open chest cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3mlkg(-1) hypertonic saline-dextran. Methylene blue was then administered as bolus of 2.5mgkg(-1) over 20 min, followed by 1.5mgkg(-1) infusion over 40 min. Historical data from 21 animals were used as control (no MB). Hemodynamic parameters, myocardial injury (troponin I), and short-term survival (3-h) were evaluated. Histopathological evaluation of heart specimens was performed. RESULTS: There were no differences between male and female animals in survival or resuscitation rate. After CA female piglets had significantly greater systolic and mean arterial pressures, and had lower troponin I plasma concentrations compared to male piglets, with or without MB. No difference was observed in histopathological analysis of heart specimens between sexes. CONCLUSIONS: After resuscitation from hypovolemic CA, female sex protects against cardiac injury, independent of sex hormones. Modulation of NO expression with MB does not improve survival or myocardial histological injury in either sex.

Neuroprotective effects of 17ß-estradiol after hypovolemic cardiac arrest in immature piglets: the role of nitric oxide and peroxidation.

We recently reported that cerebral and cardiac injuries are mitigated in immature female piglets after severe hemorrhage with subsequent cardiac arrest. Female sex was also associated with a smaller increase in the cerebral expression of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). In the current study, we tested the hypothesis that exogenously administered 17ß-estradiol (E2) can improve neurological outcome by NOS modulation. Thirty-nine sexually immature piglets were bled to a mean arterial pressure of 35 mmHg over 15 min. Fifty micrograms per kilogram of E2 was then administered to 10 male and 10 female animals (estradiol group), whereas control animals (n = 10 males and 9 females) received equal volume of normal saline. The animals were then subjected to ventricular fibrillation (4 min) followed by up to 15 min of open-chest cardiopulmonary resuscitation. Vasopressin 0.4 U · kg⁻¹ and amiodarone 0.5 mg · kg⁻¹ were given, and 3 mL · kg⁻¹ of 7.5% saline with 6% dextran was administered over 20 min. All surviving animals were killed after 3 h, and their brains examined for histological injury and NOS expression. No significant differences were observed in survival or hemodynamics between the groups. 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 a significant correlation between nNOS and iNOS levels and neuronal injury. Interestingly, estradiol attenuated cerebral damage (including lower activation of nNOS and iNOS) both in male and female piglets. In conclusion, in our immature piglet model of hypovolemic cardiac arrest, E2 downregulates iNOS and nNOS expression and results in decreased blood-brain-barrier permeability disruption and smaller neuronal injury.

Sex differences in cardiac injury after severe haemorrhage and ventricular fibrillation in pigs.

AIM OF THE STUDY: Experimental studies have shown sex differences in haemodynamic response and outcome after trauma and haemorrhagic shock. We recently reported that female sex protects against cerebral injury after exsanguination cardiac arrest (CA), independent of sexual effects of hormones. The current study examines if female sex is also cardioprotective. METHODS: In this study 21 sexually immature piglets (12 males and 9 females) were subjected to 5 min of haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3 ml kg(-1) hypertonic saline-dextran (HSD) solution for 20 min. Sexually immature animals were used to differentiate innate sex differences from the effects of sexual hormones. Sex differences in haemodynamics, myocardial injury (troponin I), and short-term survival (3-h) were evaluated. RESULTS: After resuscitation female animals had a higher blood pressure, lower heart rate, lower troponin I concentrations, and higher survival rate (100% and 63% in 3 h) despite comparable sex hormone levels. CONCLUSIONS: After resuscitation from haemorrhage and circulatory arrest, haemodynamic parameters are better preserved and myocardial injury is smaller in female piglets. This difference in outcome is independent of sexual hormones.