Temperature management during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

In addition to attaining complete or near complete cytoreduction, the instillation of select heated chemotherapeutic agents into the abdominal cavity has offered a chance for cure or longer survival inpatients with peritoneal surface malignancies. While the heating of chemotherapeutic agents enhances cytotoxicity, the resulting systemic hyperthermia has been associated with an increased risk of severe hyperthermia and its associated complications. Factors that have been associated with an increased risk of severe hyperthermia include intraoperative blood transfusions and longer perfusion duration. However, the development of severe hyperthermia still remains largely unpredictable. Thus, at several institutions, cooling protocols are employed during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Cooling protocols for CRS-HIPEC are not standardized and may be associated with episodes of severe hyperthermia or alternatively hypothermia. In theory, excessive cooling could result in a decreased effectiveness of the intraperitoneal chemotherapeutic agents. This presumption has been supported by a recent study of 214 adults undergoing CRS-HIPEC, where failure to attain a temperature of 38° C at the end of chemo-perfusion was associated with worse survival. Although not statistically significant, failure to maintain a temperature of 38° C for at least 30 minutes was associated with worse survival. Although studies are limited in this regard, the importance of maintaining a steady state of temperature during the hyperthermic phase of intraperitoneal chemotherapy administration cannot be disregarded. The following article describes the processes and physiological mechanisms responsible for hyperthermia during CRS-HIPEC. The challenges associated with temperature management during CRS-HIPEC and methods to avoid severe hypothermia and hyperthermia are also described

Postoperative Pulmonary Complications in the Morbidly Obese: The Role of Tidal Volume and the Type of Abdominal Surgery

BACKGROUND: The patient who is morbidly obese is not adequately represented in the evidence recommending intraoperative low tidal volume (V(T)) ventilation. We aimed to explore the association between V(T) adjusted for ideal body weight (IBW) and the occurrence of postoperative pulmonary complications in subjects who were morbidly obese and undergoing abdominal surgery, as well as its implications on intraoperative ventilatory variables. METHODS: We included 734 subjects with a body mass index of at least 40 kg/m(2), undergoing open or laparoscopic abdominal surgery that lasted for at least 120 min. Clinical variables were obtained to estimate the preoperative pulmonary risk as well as intraoperative ventilator data to perform associations. Outcomes were defined by medical billing code diagnoses and oxygen use. All data were collected electronically by using Structured Query Language. RESULTS: The subjects received a mean V(T)/IBW of 9.41 mL/kg IBW, and postoperative pulmonary complications occurred in 7.5% of the subjects. The occurrence of complications was correlated with the presence of several preoperative risk factors for postoperative pulmonary complications. V(T)/IBW was not associated with postoperative pulmonary complications. This finding remained present after separating different levels of V(T)/IBW. In a multivariate analysis, only laparoscopic surgery was an independent protective factor against postoperative pulmonary complications (odds ratio 0.07, 95% CI 0.01-0.55). CONCLUSIONS: V(T)/IBW was not associated with the occurrence of postoperative pulmonary complications in subjects who were morbidly obese and undergoing prolonged abdominal surgery. Future prospective studies are indicated to guide the optimum ventilation strategy for patients who are morbidly obese

Prehabilitation in Adults Undergoing Cancer Surgery: A Comprehensive Review on Rationale, Methodology, and Measures of Effectiveness

Cancer surgery places a significant burden on a patients’ functional status and quality of life. In addition, cancer surgery is fraught with postoperative complications, themselves influenced by a patient’s functional status. Prehabilitation is a unimodal or multimodal strategy that aims to increase a patient’s functional capacity to reduce postoperative complications and improve postoperative recovery and quality of life. In most cases, it involves exercise, nutrition, and anxiety-reducing interventions. The impact of prehabilitation has been explored in several types of cancer surgery, most commonly colorectal and thoracic. Overall, the existing evidence suggests prehabilitation improves physiological outcomes (e.g., lean body mass, maximal oxygen consumption) as well as clinical outcomes (e.g., postoperative complications, quality of life). Notably, the benefit of prehabilitation is additional to that of enhanced recovery after surgery (ERAS) programs. While safe, prehabilitation programs require multidisciplinary coordination preoperatively. Despite the existence of numerous systematic reviews and meta-analyses, the certainty of evidence demonstrating the efficacy and safety of prehabilitation is low to moderate, principally due to significant methodological heterogeneity and small sample sizes. There is a need for more large-scale multicenter randomized controlled trials to draw strong clinical recommendations

The Role of Hyperthermia in the Treatment of Peritoneal Surface Malignancies

PURPOSE OF REVIEW: Hyperthermia is used to treat peritoneal surface malignancies (PSM), particularly during hyperthermic intraperitoneal chemotherapy (HIPEC). This manuscript provides a focused update of hyperthermia in the treatment of PSM. RECENT FINDINGS: The heterogeneous response to hyperthermia in PSM can be explained by tumor and treatment conditions. PSM tumors may resist hyperthermia via metabolic and immunologic adaptation. The thermodynamics of HIPEC are complex and require computational fluid dynamics (CFD). The clinical evidence supporting the benefit of hyperthermia is largely observational. Continued research will allow clinicians to characterize and predict the individual response of PSM to hyperthermia. The application of hyperthermia in current HIPEC protocols is mostly empirical. Thus, modeling heat transfer with CFD is a necessary task if we are to achieve consistent and reproducible hyperthermia. Although observational evidence suggests a survival benefit of hyperthermia, no clinical trial has tested the individual role of hyperthermia in PSM

Preventing Prolonged Times to Awakening While Mitigating the Risk of Patient Awareness: Gas Man Computer Simulations of Sevoflurane Consumption From Brief, High Fresh Gas Flow Before the End of Surgery

Prolonged times to tracheal extubation are associated with adverse patient and economic outcomes. We simulated awakening patients from sevoflurane after long-duration surgery at 2% end-tidal concentration, 1.0 minimum alveolar concentration (MAC) in a 40-year-old. Our end-of-surgery target was 0.5 MAC, the Michigan Awareness Control Study's threshold for intraoperative alerts. Consider an anesthetist who uses a 1 liter/minute gas flow until surgery ends. During surgical closure, the inspired sevoflurane concentration is reduced from 2.05% to 0.62% (i.e., MAC-awake). The estimated time to reach 0.5 MAC is 28 minutes. From a previous study, 28 minutes exceeded ≥95% of surgical closure times for all 244 distinct surgical procedures (N=23,343 cases). Alternatively, the anesthetist uses 8 liters/minute gas flow with the vaporizer at MAC-awake for 1.8 minutes, which reduces the end-tidal concentration to 0.5 MAC. The anesthetist then increases the vaporizer to keep end-tidal 0.5 MAC until the surgery ends. An additional simulation shows that, compared with simulated end-tidal agent feedback control, this approach consumed 0.45 mL extra agent. Simulation results are the same for an 80-year-old patient. The extra 0.45 mL has a global warming potential comparable to driving 26 seconds at 40 kilometers (25 miles) per hour, comparable to route modification to avoid potential roadway hazards

Is Greater Than 0.5 MAC Inhalational Agent Use Post-Bypass Related to Need for Inotropic and/or Vasoconstrictor Support?

Background and Aims: We hypothesized that maintaining a patient on moderate–high doses of potent inhalational agent for greater than 30 min during the post-bypass period would be an independent predictor of initiation and usage of either inotropic and/or vasopressor infusions. Setting and Design: This study is a retrospective design and approved by the institutional review board. The setting was a single-center, academic tertiary care hospital in Detroit, Michigan. Materials and Methods: Three-hundred, ninety-seven elective cardiac surgery patients were identified for chart review. Electronic medical records were reviewed to collect demographics and perioperative data. Statistics used include a propensity score regression adjusted analysis utilizing logistic regression models and a multivariable model. Results: A propensity score regression adjusted analysis was performed and then applied in both univariate and multivariate logistic regression models with a p value of <0.05 reaching statistical significance. Fifty-six percent of the participants had an exposure of greater than 30 min of a minimum alveolar concentration of isoflurane greater than 0.5 (ETISO ≥ 0.5MAC, 30 min) in the post-bypass period. After adjusting for propensity score, this was found to be a significant predictor of inotrope and/or vasoconstrictor use post-bypass (OR 2.49, 95% CI 1.15–5.38, p = 0.021). In the multivariate model, pulmonary hypertension (OR 5.9; 95% CI 1.33–26.28; p = 0.02), Euroscore II (2.73; 95% CI 1.35–5.5; p = 0.005), and cardiopulmonary bypass hours (OR 1.86; 95% CI 1.02–3.4; p = 0.042) emerged as significant. Conclusions: This study showed that an ETISO ≥ 0.5MAC, 30 min exposure during the immediate post-bypass period during elective cardiac surgery was an independent predictor of a patient being started on inotrope or vasoconstrictor infusions. Further research should consider a prospective design and examine depth of anesthesia during the post-bypass period

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis

Stress neuropeptide levels in adults with chest pain due to coronary artery disease: potential implications for clinical assessment

: Substance P (SP) and neuropeptide Y (NPY) are neuropeptides involved in nociception. The study of biochemical markers of pain in communicating critically ill coronary patients may provide insight for pain assessment and management in critical care. Purpose of the study was to to explore potential associations between plasma neuropeptide levels and reported pain intensity in coronary critical care adults, in order to test the reliability of SP measurements for objective pain assessment in critical care