Ventilatory efficiency as a prognostic factor for postoperative complications in patients undergoing elective major surgery: a systematic review.

BACKGROUND: Major surgery is associated with high complication rates. Several risk scores exist to assess individual patient risk before surgery but have limited precision. Novel prognostic factors can be included as additional building blocks in existing prediction models. A candidate prognostic factor, measured by cardiopulmonary exercise testing, is ventilatory efficiency (VE/VCO2). The aim of this systematic review was to summarise evidence regarding VE/VCO2 as a prognostic factor for postoperative complications in patients undergoing major surgery. METHODS: A medical library specialist developed the search strategy. No database-provided limits, considering study types, languages, publication years, or any other formal criteria were applied to any of the sources. Two reviewers assessed eligibility of each record and rated risk of bias in included studies. RESULTS: From 10,082 screened records, 65 studies were identified as eligible. We extracted adjusted associations from 32 studies and unadjusted from 33 studies. Risk of bias was a concern in the domains 'study confounding' and 'statistical analysis'. VE/VCO2 was reported as a prognostic factor for short-term complications after thoracic and abdominal surgery. VE/VCO2 was also reported as a prognostic factor for mid- to long-term mortality. Data-driven covariable selection was applied in 31 studies. Eighteen studies excluded VE/VCO2 from the final multivariable regression owing to data-driven model-building approaches. CONCLUSIONS: This systematic review identifies VE/VCO2 as a predictor for short-term complications after thoracic and abdominal surgery. However, the available data do not allow conclusions about clinical decision-making. Future studies should select covariables for adjustment a priori based on external knowledge. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022369944).

Blood volume and hemodynamics during treatment of major hemorrhage with Ringer solution, 5% albumin, and 20% albumin: a single-center randomized controlled trial.

BACKGROUND: Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable option to maintain the blood volume during surgery associated with major hemorrhage. Therefore, the aim of this study was to quantify and compare the plasma volume expansion properties of 5% albumin, 20% albumin, and Ringer-lactate, when infused during major surgery. METHODS: In this single-center randomized controlled trial, fluid replacement therapy to combat hypovolemia during the hemorrhagic phase of cystectomy was randomly allocated in 42 patients to receive either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min at the beginning of the hemorrhagic phase, both completed by a Ringer-lactate replacing blood loss in a 1:1 ratio, or Ringer-lactate alone to replace blood loss in a 3:1 ratio. Measurements of blood hemoglobin over 5 h were used to estimate the effectiveness of each fluid to expand the blood volume using the following regression equation: blood loss plus blood volume expansion = factor + volume of infused albumin + volume of infused Ringer-lactate. RESULTS: The median hemorrhage was 848 mL [IQR: 615-1145]. The regression equation showed that the Ringer-lactate solution expanded the plasma volume by 0.18 times the infused volume while the corresponding power of 5% and 20% albumin was 0.74 and 2.09, respectively. The Ringer-lactate only fluid program resulted in slight hypovolemia (mean, - 313 mL). The 5% and 20% albumin programs were more effective in filling the vascular system; this was evidenced by blood volume changes of only + 63 mL and - 44 mL, respectively, by long-lasting plasma volume expansion with median half time of 5.5 h and 4.8 h, respectively, and by an increase in the central venous pressure. CONCLUSION: The power to expand the plasma volume was 4 and almost 12 times greater for 5% albumin and 20% albumin than for Ringer-lactate, and the effect was sustained over 5 h. The clinical efficacy of albumin during major hemorrhage was quite similar to previous studies with no hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov NCT05391607, date of registration May 26, 2022.

Diagnostic Value of Urine Cytology in Pharmacologically Forced Diuresis for Upper Tract Urothelial Carcinoma Diagnosis and Follow-Up.

We performed a urine cytology analysis of a pharmacologically induced diuresis for the diagnosis of upper tract urothelial carcinoma. To evaluate the diagnostic value of cytology of pharmacologically forced diuresis, an initial cohort of 77 consecutive patients with primary upper tract urothelial carcinoma treated via radical surgery was enrolled. To evaluate pharmacologically forced diuresis cytology as a follow-up procedure, a second cohort of 1250 patients who underwent a radical cystectomy for bladder cancer was selected. In the first cohort, the sensitivity of cytology of pharmacologically forced diuresis in patients with invasive, high-grade, low-grade, and concomitant carcinoma in situ was 8%, 9%, 0%, and 14%, respectively. In the second cohort, cytology of pharmacologically forced diuresis was positive in 30/689 (4.3%) patients, in whom upper urinary tract recurrence was present in 21/30 (70%) of cases, and urethral recurrence was present in 8/30 (26%) of cases. As a follow-up tool, cytology of pharmacologically forced diuresis showed a sensitivity, specificity, and positive and negative predictive values of 60%, 99%, 70%, and 98%, respectively. Overall, as a diagnostic tool, the sensitivity of cytology of pharmacologically forced diuresis is slightly better in patients with invasive upper tract urothelial carcinoma and concomitant carcinoma in situ. As a follow-up method, positive cytology of pharmacologically forced diuresis is strongly related to cancer recurrence and can reveal urethral recurrence. Cytology of pharmacologically forced diuresis might be useful in cases with contraindications for imaging or when achieving endoscopic access to the upper urinary tract is difficult.

Sex Does Not Affect Survival: A Propensity Score-Matched Comparison in a Homogenous Contemporary Radical Cystectomy Cohort.

OBJECTIVES: To determine whether biological sex affects oncological outcome after extended pelvic lymph node dissection, radical cystectomy, and urinary diversion for muscle-invasive bladder cancer, and to identify risk factors impacting outcome. PATIENTS AND METHODS: We performed a single-center, retrospective observational cohort study with prospective data collection with a propensity score matched population. A total of 1165 consecutive patients from 2000 to 2020, (317 women and 848 men) scheduled for open extended pelvic lymph node dissection, radical cystectomy, and urinary diversion for urothelial bladder cancer were included in the final analysis. Overall Survival (OS), Cancer-Specific-Survival (CSS), and Recurrence-Free-survival (RFS) were assessed with multivariable weighted Cox regression analysis as well as with propensity score matched Cox-Regression. RESULTS: No significant difference was found between sexes regarding OS (HR 1.18, [0.93-1.49], P = .16), CSS (HR 0.87, [0.64-1.18], P = .38), or RFS (HR 0.80, [0.59-1.07], P = .13). These results were confirmed after propensity score matching: female sex was not associated with inferior OS (HR 1.20, [0.91-1.60], P = .19), CSS (HR 1.01, [0.75-1.35], P = .97) or RFS (HR 0.98, [0.75-1.27], P = .86). CONCLUSIONS: We did not find a significant difference in cancer-related outcomes or overall survival after extended pelvic lymph node dissection, open radical cystectomy, and urinary diversion for urothelial cancer between males and females even after adjustment with propensity matching score for multiple factors including oncological parameters, smoking status, and renal function.

Functional Impact of Neuro-Vascular Bundle Preservation in High Risk Prostate Cancer without Compromising Oncological Outcomes: A Propensity-Modelled Analysis.

Nerve sparing (NS) is a surgical technique to optimize functional outcomes of radical prostatectomy (RP). However, it is not recommended in high risk (HR) cases because of the risk of a positive surgical margin that may increase the risk of cancer recurrence. In the last two decades there has been a change of perspective to the effect that in well-selected cases NS could be an oncologically safe option with better functional outcomes. Therefore, we aim to compare the functional outcomes and oncological safety of NS during RP in men with HR disease. A total of 1340 patients were included in this analysis, of which 12% (n = 158) underwent non-NSRP and 39% (n = 516) and 50% (n = 666) uni- and bilateral NSRP, respectively. We calculated a propensity score and used inverse probability of treatment weighting (IPTW) to balance the baseline characteristics of Pca patients undergoing non-NSRP and those having uni- and bilateral NSRP, respectively. NS improved functional outcomes; after IPTW, only 3% of patients having non-NSRP reached complete erectile function recovery (without erectile aid) at 24 months, whereas 22% reached erectile function recovery (with erectile aid), while 87% were continent. Unilateral NS increased the probability of functional recovery in all outcomes (OR 1.1 or 1.2, respectively), bilateral NS slightly more so (OR 1.1 to 1.4). NSRP did not impact the risk of any recurrence (HR 0.99, 95%CI 0.73-1.34, p = 0.09), and there was no difference in survival for men who underwent NSRP (HR 0.65, 95%CI 0.39-1.08). There was no difference in cancer-specific survival (0.56, 95%CI 0.29-1.11). Our study found that NSRP significantly improved functional outcomes and can be safely performed in carefully selected patients with HR-PCa without compromising long term oncological outcomes.

The Role of Intraoperative and Early Postoperative Blood Pressure Variations, Fluid Balance and Inotropics in Fibula Free Flap Head and Neck Reconstruction: A Retrospective Analysis.

BACKGROUND: In head and neck reconstructive surgery, postoperative complications are a well-known concern. METHODS: We examined 46 patients who underwent ablative surgery and received fibula free flap reconstruction. The main focus was to assess the influence of intraoperative blood pressure fluctuations and the administration of inotropic drugs on complications, either related to the flap or systemic, serving as the primary endpoint. RESULTS: Utilizing logistic regression models, we identified that intraoperative mean arterial blood pressure (MAP) drops did not correlate with the occurrence of either flap-related complications (MAP < 70, p = 0.79; MAP < 65, p = 0.865; MAP < 60, p = 0.803; MAP < 55, p = 0.937) or systemic medical complications (MAP < 70, p = 0.559; MAP < 65, p = 0.396; MAP < 60, p = 0.211; MAP < 55, p = 0.936). The occurrence of flap-related complications significantly increased if a higher dosage of dobutamine was administered (median 27.5 (IQR 0-47.5) vs. 62 (38-109) mg, p = 0.019) but not if norepinephrine was administered (p = 0.493). This correlation was especially noticeable given the uptick in complications associated with fluid overload (3692 (3101-4388) vs. 4859 (3555-6216) mL, p = 0.026). CONCLUSION: Intraoperative and immediate postoperative blood pressure fluctuations are common but are not directly associated with flap-related complications; however, dobutamine application as well as fluid overload may impact flap-specific complications.

Concentrated urine, low urine flow, and postoperative elevation of plasma creatinine: A retrospective analysis of pooled data.

Elevations of plasma creatinine are common after major surgery, but their pathophysiology is poorly understood. To identify possible contributing mechanisms, we pooled data from eight prospective studies performed in four different countries to study circumstances during which elevation of plasma creatinine occurs. We included 642 patients undergoing mixed major surgeries, mostly open gastrointestinal. Plasma and urinary creatinine and a composite index for renal fluid conservation (Fluid Retention Index, FRI) were measured just before surgery and on the first postoperative morning. Urine flow was measured during the surgery. The results show that patients with a postoperative increase in plasma creatinine by >25% had a high urinary creatinine concentration (11.0±5.9 vs. 8.3±5.6 mmol/L; P< 0001) and higher FRI value (3.2±1.0 vs. 2.9±1.1; P< 0.04) already before surgery was initiated. Progressive increase of plasma creatinine was associated with a gradually lower urine flow and larger blood loss during the surgery (Kruskal-Wallis test, P< 0.001). The patients with an elevation > 25% also showed higher creatinine and a higher FRI value on the first postoperative morning (P< 0.001). Elevations to > 50% of baseline were associated with slightly lower mean arterial pressure (73 ± 10 vs. 80 ± 12 mmHg; P< 0.005). We conclude that elevation of plasma creatinine in the perioperative period was associated with low urine flow and greater blood loss during surgery and with concentrated urine both before and after the surgery. Renal water conservation-related mechanisms seem to contribute to the development of increased plasma creatinine after surgery.

Impact of Intraoperative Fluid Balance and Norepinephrine on Postoperative Acute Kidney Injury after Cystectomy and Urinary Diversion over Two Decades: A Retrospective Observational Cohort Study.

The use of norepinephrine and the restriction of intraoperative hydration have gained increasing acceptance over the last few decades. Recently, there have been concerns regarding the impact of this approach on renal function. The objective of this study was to examine the influence of norepinephrine, intraoperative fluid administration and their interaction on acute kidney injury (AKI) after cystectomy. In our cohort of 1488 consecutive patients scheduled for cystectomies and urinary diversions, the overall incidence of AKI was 21.6% (95%-CI: 19.6% to 23.8%) and increased by an average of 0.6% (95%-CI: 0.1% to 1.1%, p = 0.025) per year since 2000. The fluid and vasopressor regimes were characterized by an annual decrease in fluid balance (-0.24 mL·kg-1·h-1, 95%-CI: -0.26 to -0.22, p < 0.001) and an annual increase in the amount of norepinephrine of 0.002 µg·kg-1·min-1 (95%-CI: 0.0016 to 0.0024, p < 0.001). The interaction between the fluid balance and norepinephrine levels resulted in a U-shaped association with the risk of AKI; however, the magnitude and shape depended on the reference categories of confounders (age and BMI). We conclude that decreased intraoperative fluid balance combined with increased norepinephrine administration was associated with an increased risk of AKI. However, other potential drivers of the observed increase in AKI incidence need to be further investigated in the future.

Opioid-Free Anesthesia for Open Radical Cystectomy Is Feasible and Accelerates Return of Bowel Function: A Matched Cohort Study.

The aim of this study was to evaluate the feasibility of opioid-free anesthesia (OFA) in open radical cystectomy (ORC) with urinary diversion and to assess the impact on recovery of gastrointestinal function. We hypothesized that OFA would lead to earlier recovery of bowel function. A total of 44 patients who underwent standardized ORC were divided into two groups (OFA group vs. control group). In both groups, patients received epidural analgesia (OFA group: bupivacaine 0.25%, control group: bupivacaine 0.1%, fentanyl 2 mcg/mL, and epinephrine 2 mcg/mL). The primary endpoint was time to first defecation. Secondary endpoints were incidence of postoperative ileus (POI) and incidence of postoperative nausea and vomiting (PONV). The median time to first defecation was 62.5 h [45.8-80.8] in the OFA group and 118.5 h [82.6-142.3] (p < 0.001) in the control group. With regard to POI (OFA group: 1/22 patients (4.5%); control group: 2/22 (9.1%)) and PONV (OFA group: 5/22 patients (22.7%); control group: 10/22 (45.5%)), trends but no significant results were found (p = 0.99 and p = 0.203, respectively). OFA appears to be feasible in ORC and to improve postoperative functional gastrointestinal recovery by halving the time to first defecation compared with standard fentanyl-based intraoperative anesthesia.

Multimodal prehabilitation for major surgery in elderly patients to lower complications: protocol of a randomised, prospective, multicentre, multidisciplinary trial (PREHABIL Trial).

INTRODUCTION: The global volume of surgery is growing and the population ageing, and economic pressure is rising. Major surgery is associated with relevant morbidity and mortality. Postoperative reduction in physiological and functional capacity is especially marked in the elderly, multimorbid patient with low fitness level, sarcopenia and malnutrition. Interventions aiming to optimise the patient prior to surgery (prehabilitation) may reduce postoperative complications and consequently reduce health costs. METHODS AND ANALYSIS: This is a multicentre, multidisciplinary, prospective, 2-arm parallel-group, randomised, controlled trial with blinded outcome assessment. Primary outcome is the Comprehensive Complications Index at 30 days. Within 3 years, we aim to include 2×233 patients with a proven fitness deficit undergoing major surgery to be randomised using a computer-generated random numbers and a minimisation technique. The study intervention consists of a structured, multimodal, multidisciplinary prehabilitation programme over 2-4 weeks addressing deficits in physical fitness and nutrition, diabetes control, correction of anaemia and smoking cessation versus standard of care. ETHICS AND DISSEMINATION: The PREHABIL trial has been approved by the responsible ethics committee (Kantonale Ethikkomission Bern, project ID 2020-01690). All participants provide written informed consent prior to participation. Participant recruitment began in February 2022 (10 and 8 patients analysed at time of submission), with anticipated completion in 2025. Publication of the results in peer-reviewed scientific journals are expected in late 2025. TRIAL REGISTRATION NUMBER: NCT04461301.

A Systematic Review of Intra- and Postoperative Complication Reporting and Grading in Urological Surgery: Understanding the Pitfalls and a Path Forward.

CONTEXT: Surgical outcomes and patient morbidity are often surrogate markers of health care quality and efficiency. These parameters can only be used with confidence if the reporting and grading of intra- and postoperative complications are reliable and reproducible. Without uniformity and regulation, the risk of under-reporting, and thus significant underestimation of the burden of intra- and postoperative morbidity, is high and should be of great concern to the international surgical community. OBJECTIVE: To assess the quality and utility of currently available reporting and classification systems for intra- and postoperative complications, recognise their advantages and pitfalls, discuss the overall implications of these systems for urological surgery, and identify potential solutions for future reporting and classification systems. EVIDENCE ACQUISITION: A comprehensive search was performed using multiple reputable databases and trial registries up to October 25, 2022. Only studies that adhered to predefined inclusion criteria were included. Study selection and data extraction were independently performed by two review authors. The review was performed according to strict methodological guidelines in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. EVIDENCE SYNTHESIS: A total of 13 papers highlighting 13 various complication systems were critically assessed in this review. All studies proposed an intra- or postoperative complication reporting or grading system that was surgically related. At present, there is no single instrument in clinical practice to account for all relevant complication data. Six of the 13 studies were clinically validated (46%) and only three studies were urology-focused (23%). Meta-analysis was not possible. CONCLUSIONS: Current individual complication tools are flawed, so there is a need for a novel, all-inclusive, specialty-specific reporting and classification system for intra- and postoperative complications. If successfully validated and integrated worldwide, such an instrument would have the potential to play a significant role in reshaping efficiency in health care systems and improving surgical and patient quality of care. PATIENT SUMMARY: Current tools for reporting and classifying complications during and after surgery underestimate how burdensome such complications can be for patients. We summarise the reporting and classification tools currently available, discuss their advantages and drawbacks, and propose potential solutions for future systems. Our review can help in better understanding the changes required for future tools and how to improve overall surgical outcomes for patients.

Fully Closed-Loop Insulin Delivery in Patients Undergoing Pancreatic Surgery.

The central role of pancreas in glucose regulation imposes high demands on perioperative glucose management in patients undergoing pancreatic surgery. In a post hoc subgroup analysis of a randomized controlled trial, we evaluated the perioperative use of subcutaneous (SC) fully closed-loop (FCL; CamAPS HX) versus usual care (UC) insulin therapy in patients undergoing partial or total pancreatic resection. Glucose control was compared using continuous glucose monitoring (CGM) metrics (% time with CGM values between 5.6 and 10.0 mmol/L and more). Over the time of hospitalization, FCL resulted in better glucose control than UC with more time spent in the target range 5.6-10.0 mmol/L (mean [standard deviation] % time in target 77.7% ± 4.6% and 41.1% ± 19.5% in FCL vs. UC subjects, respectively; mean difference 36.6% [95% confidence interval 18.5-54.8]), without increasing the risk of hypoglycemia. Findings suggest that an adaptive SC FCL approach effectively accommodated the highly variable insulin needs in patients undergoing pancreatic surgery. Clinical trials registration: ClinicalTrials.gov, NCT04361799.