Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial.

BACKGROUND: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. METHODS: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. RESULTS: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. CONCLUSIONS: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. CLINICAL TRIAL REGISTRATION: NCT03021525.

An educational intervention to reduce the incidence of postoperative residual curarisation: a cluster randomised crossover trial in patients undergoing general anaesthesia.

BACKGROUND: The incidence of postoperative residual curarisation remains unacceptably high. We assessed whether an educational intervention on perioperative neuromuscular block management can reduce it. METHODS: In this multicentre, cluster randomised crossover trial, centres were allocated to receive an educational intervention either in a first or a second period. The educational intervention consisted of a lecture about neuromuscular management key points, including quantitative neuromuscular monitoring and use of reversal agents. The lecture was streamed to allow repetition. Additionally, memory cards were distributed in each operating theatre. The primary outcome was postoperative residual curarisation in the PACU. Secondary outcomes were frequency of quantitative neuromuscular monitoring, use of reversal agents, and incidence of postoperative pulmonary complications during hospital stay. Measurements were performed before randomisation and after the first and the second period. The effect of the educational intervention was estimated using multivariable mixed effects logistic regression models. RESULTS: We included 2314 subjects in 34 Spanish centres. Postoperative residual curarisation incidence was not affected by the educational intervention (odds ratio [OR] 0.90 [95% confidence interval {CI}: 0.51-1.58]; P=0.717 and 1.30 [0.73-2.30]; P=0.371] for first and second time-period interaction). The educational intervention increased the quantitative neuromuscular monitor usage (OR 2.04 [95% CI: 1.31-3.19]; P=0.002), the use of reversal agents was unchanged (OR 0.79 [95% CI: 0.50-1.26]; P=0.322), and the incidence of postoperative pulmonary complications decreased (OR 0.19 [95% CI: 0.10-0.35]; P<0.001). CONCLUSIONS: An educational intervention on perioperative neuromuscular block management did not reduce the incidence of postoperative residual curarisation nor increase reversal, despite increased quantitative neuromuscular monitoring. Sugammadex reversal was associated with reduced postoperative residual curarisation. The educational intervention was associated with a decrease in postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03128151.

Quality of Recovery and Innate Immune Homeostasis in Patients Undergoing Low-pressure Versus Standard-pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery (RECOVER): A Randomized Controlled Trial.

OBJECTIVE: To study the effects of intra-abdominal pressure on the quality of recovery and innate cytokine production capacity after laparoscopic colorectal surgery within the enhanced recovery after surgery program. BACKGROUND: There is increasing evidence for the safety and advantages of low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade (NMB). Nonetheless, there is a weak understanding of the relationship between clinical outcomes, surgical injury, postoperative immune dysfunction, and infectious complications. METHODS: Randomized controlled trial of 178 patients treated at standard-pressure pneumoperitoneum (12 mm Hg) with moderate NMB (train-of-four 1-2) or low pressure (8 mm Hg) facilitated by deep NMB (posttetanic count 1-2). The primary outcome was the quality of recovery (Quality of Recovery 40 questionnaire) on a postoperative day 1 (POD1). The primary outcome of the immune substudy (n=100) was ex vivo tumor necrosis factor α production capacity upon endotoxin stimulation on POD1. RESULTS: Quality of Recovery 40 score on POD1 was significantly higher at 167 versus 159 [mean difference (MD): 8.3 points; 95% confidence interval (CI): 2.5, 14.1; P =0.005] and the decline in cytokine production capacity was significantly less for tumor necrosis factor α and interleukin-6 (MD: -172 pg/mL; 95% CI: -316, -27; P =0.021 and MD: -1282 pg/mL; 95% CI: -2505, -59; P =0.040, respectively) for patients operated at low pressure. Low pressure was associated with reduced surgical site hypoxia and inflammation markers and circulating damage-associated molecular patterns, with a less impaired early postoperative ex vivo cytokine production capacity. At low pressure, patients reported lower acute pain scores and developed significantly less 30-day infectious complications. CONCLUSIONS: Low intra-abdominal pressure during laparoscopic colorectal surgery is safe, improves the postoperative quality of recovery and preserves innate immune homeostasis, and forms a valuable addition to future enhanced recovery after surgery programs.

European Neuromuscular Centre consensus statement on anaesthesia in patients with neuromuscular disorders.

BACKGROUND AND PURPOSE: Patients with neuromuscular conditions are at increased risk of suffering perioperative complications related to anaesthesia. There is currently little specific anaesthetic guidance concerning these patients. Here, we present the European Neuromuscular Centre (ENMC) consensus statement on anaesthesia in patients with neuromuscular disorders as formulated during the 259th ENMC Workshop on Anaesthesia in Neuromuscular Disorders. METHODS: International experts in the field of (paediatric) anaesthesia, neurology, and genetics were invited to participate in the ENMC workshop. A literature search was conducted in PubMed and Embase, the main findings of which were disseminated to the participants and presented during the workshop. Depending on specific expertise, participants presented the existing evidence and their expert opinion concerning anaesthetic management in six specific groups of myopathies and neuromuscular junction disorders. The consensus statement was prepared according to the AGREE II (Appraisal of Guidelines for Research & Evaluation) reporting checklist. The level of evidence has been adapted according to the SIGN (Scottish Intercollegiate Guidelines Network) grading system. The final consensus statement was subjected to a modified Delphi process. RESULTS: A set of general recommendations valid for the anaesthetic management of patients with neuromuscular disorders in general have been formulated. Specific recommendations were formulated for (i) neuromuscular junction disorders, (ii) muscle channelopathies (nondystrophic myotonia and periodic paralysis), (iii) myotonic dystrophy (types 1 and 2), (iv) muscular dystrophies, (v) congenital myopathies and congenital dystrophies, and (vi) mitochondrial and metabolic myopathies. CONCLUSIONS: This ENMC consensus statement summarizes the most important considerations for planning and performing anaesthesia in patients with neuromuscular disorders.

Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

PURPOSE OF REVIEW: Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action. RECENT FINDINGS: We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting. We found consistent preclinical evidence of a potential action of MNTX and NTX on cancer growth and spread mediated mainly by effect on the opioid growth factor receptor (OGFr) axis, which results in depressed cell replication. However, clinical results are scarce and limited to poor-quality evidence. Further high-quality studies are warranted to study antagonists of mu-opioid receptor role as a therapeutic option in different types of cancer, especially in patients where the classical treatment causes unacceptable side effects.

A multimodal prehabilitation program for the reduction of post-operative complications after surgery in advanced ovarian cancer under an ERAS pathway: a randomized multicenter trial (SOPHIE).

BACKGROUND: Multimodal prehabilitation programs that combine exercise training, nutritional support, and optimize psychological status have demonstrated efficacy in reducing post-operative complications in non-gynecological abdominal surgeries; however, the benefit in advanced ovarian cancer is unclear. PRIMARY OBJECTIVE: To compare the post-operative complications of a multimodal prehabilitation program in patients undergoing cytoreductive surgery for advanced ovarian cancer with standard pre-operative care. STUDY HYPOTHESIS: Multimodal prehabilitation reduces post-operative complications in patients undergoing cytoreductive surgery for advanced ovarian cancer and subsequently reduces the length of hospital stay and time to initiation of adjuvant therapy. TRIAL DESIGN: This prospective, multi-institutional, randomized clinical trial will randomize candidates for surgery to either the standard of care or multimodal prehabilitation consisting of (1) 2- or 3-weekly supervised high-intensity resistance training sessions and promotion of physical activity through a mobile phone application; (2) respiratory physiotherapy; (3) nutrition counseling with supplementation as needed; and (4) weekly psychological and cognitive behavioral sessions. Baseline, pre-operative and 1 month post-operative data will be collected. An independent blinded evaluator will collect intra- and post-operative surgical data. MAJOR INCLUSION/EXCLUSION CRITERIA: Women with advanced ovarian cancer International Federation of Gynecology and Obstetrics (2014) stage III or IV scheduled to undergo primary debulking surgery, interval debulking surgery,or secondary or tertiary cytoreductive surgery will be included. Women are eligible if they are able to undergo a minimum of 2 weeks of prehabilitation prior to surgery. Patients with <75% adherence to the total program will be excluded. PRIMARY ENDPOINT: Post-operative complications in patients with advanced ovarian cancer undergoing cytoreductive surgery according to the Comprehensive Complication Index. SAMPLE SIZE: 146 patients will be included, 73 in each group. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual should be completed in December 2024 with results reported soon thereafter. TRIAL REGISTRATION NUMBER: NCT04862325.

Intraabdominal Pressure Targeted Positive End-expiratory Pressure during Laparoscopic Surgery: An Open-label, Nonrandomized, Crossover, Clinical Trial.

BACKGROUND: Pneumoperitoneum for laparoscopic surgery is associated with a rise of driving pressure. The authors aimed to assess the effects of positive end-expiratory pressure (PEEP) on driving pressure at varying intraabdominal pressure levels. It was hypothesized that PEEP attenuates pneumoperitoneum-related rises in driving pressure. METHODS: Open-label, nonrandomized, crossover, clinical trial in patients undergoing laparoscopic cholecystectomy. "Targeted PEEP" (2 cm H2O above intraabdominal pressure) was compared with "standard PEEP" (5 cm H2O), with respect to the transpulmonary and respiratory system driving pressure at three predefined intraabdominal pressure levels, and each patient was ventilated with two levels of PEEP at the three intraabdominal pressure levels in the same sequence. The primary outcome was the difference in transpulmonary driving pressure between targeted PEEP and standard PEEP at the three levels of intraabdominal pressure. RESULTS: Thirty patients were included and analyzed. Targeted PEEP was 10, 14, and 17 cm H2O at intraabdominal pressure of 8, 12, and 15 mmHg, respectively. Compared to standard PEEP, targeted PEEP resulted in lower median transpulmonary driving pressure at intraabdominal pressure of 8 mmHg (7 [5 to 8] vs. 9 [7 to 11] cm H2O; P = 0.010; difference 2 [95% CI 0.5 to 4 cm H2O]); 12 mmHg (7 [4 to 9] vs.10 [7 to 12] cm H2O; P = 0.002; difference 3 [1 to 5] cm H2O); and 15 mmHg (7 [6 to 9] vs.12 [8 to 15] cm H2O; P < 0.001; difference 4 [2 to 6] cm H2O). The effects of targeted PEEP compared to standard PEEP on respiratory system driving pressure were comparable to the effects on transpulmonary driving pressure, though respiratory system driving pressure was higher than transpulmonary driving pressure at all intraabdominal pressure levels. CONCLUSIONS: Transpulmonary driving pressure rises with an increase in intraabdominal pressure, an effect that can be counterbalanced by targeted PEEP. Future studies have to elucidate which combination of PEEP and intraabdominal pressure is best in term of clinical outcomes.

Patterns in medication incidents: A 10-yr experience of a cross-national anaesthesia incident reporting system.

BACKGROUND: Medication-related adverse events (MRE) in anaesthesia care are frequent and require a deeper understanding if we are to prevent medication harm. METHODS: We searched for reported MRE from the Spanish Anaesthesia Incident Reporting System (SENSAR) database over a 10-yr period. SENSAR is a cross-national, multicentre system focused on perioperative and critical care. A descriptive analysis of independent variables, phase of medication process, type of MRE, and medication group involved, and their relationships with morbidity was conducted. RESULTS: A total of 1970 MRE were identified from 7072 reported incidents. Patient harm was reported in 31% of the MRE. The administration phase was more frequent (42%) and showed the highest harm rate (44%) compared with other medication process phases. The most frequent types of MRE were wrong treatment regimen and wrong medication (55% of cases). The medication groups most commonly reported were those that alter haemostasis (18%), vasoconstrictor agents (13%), and opioids (10%). Vasoconstrictor agents, benzodiazepines, and neuromuscular blocking agents were the medication groups involved in patient harm four-fold more, and opioids three-fold more, than medications that alter haemostasis. The 1970 incidents were investigated and led to implementation of 4223 local corrective patient safety and quality improvement measures. CONCLUSIONS: Patient harm in the perioperative setting from medications remains a major issue for patients, hospital leaders, and clinicians. We found patterns and specific causes that can be mitigated through proven systems solutions, and should be taken into consideration in designing sustainable solutions for safe perioperative care. CLINICAL TRIAL REGISTRATION: NCT03615898.

Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy: a randomised controlled trial.

BACKGROUND: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. METHODS: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. RESULTS: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. CONCLUSIONS: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. CLINICAL TRIAL REGISTRATION: NCT02776046.

Spontaneous recovery of neuromuscular blockade is an independent risk factor for postoperative pulmonary complications after abdominal surgery: A secondary analysis.

BACKGROUND: In intermediate-to-high-risk patients, major abdominal surgery is associated with a high incidence of postoperative complications, mainly pulmonary. Neuromuscular blocking drugs have been suggested as a contributing factor, but this remains unproven. OBJECTIVE: To define the relationship of neuromuscular blockade management (reversal) with postoperative pulmonary complications (PPCs). DESIGN: The individualised PeRioperative Open-lung approach Versus standard protectivE ventilation in abdominal surgery study was a prospective, multicentre, four-arm, randomised controlled trial. This is a secondary analysis of the data. SETTING: Twenty-one teaching hospitals in Spain. The study was conducted between 2 January 2015, and 18 May 2016. PATIENTS: Age more than 18 years with an intermediate-to-high risk for PPCs, scheduled for major abdominal surgery lasting more than 2 h. Exclusion criteria included pregnancy or breastfeeding, and moderate-to-severe organ diseases. INTERVENTIONS: The mode of reversal of neuromuscular blockade determined two patient groups: pharmacological reversal versus spontaneous recovery. MAIN OUTCOME MEASURES: The primary outcome was a composite of PPCs during the first 30 postoperative days. The association between categorical variables and PPCs within 30 days was studied. Univariate and multivariable logistic regression modelling and propensity score analyses were performed. RESULTS: From the 923 patients included, 596 (64.6%) presented with PPCs within 30 days after surgery. Patients who developed these complications were older with a higher BMI, a lower pre-operative SpO2, a higher ASA physical status score and a higher incidence of arterial hypertension, diabetes mellitus or chronic obstructive pulmonary disease. Pharmacological neuromuscular blockade reversal was associated with a lower incidence of PPCs (odds ratio 0.62, 95% CI 0.47 to 0.82). CONCLUSION: Spontaneous recovery of neuromuscular blockade was an independent risk factor for PPCs in patients with intermediate-to-high risk, undergoing abdominal surgery. We suggest this factor should be included in future studies on PPCs. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02158923.

A multifaceted individualized pneumoperitoneum strategy for laparoscopic colorectal surgery: a multicenter observational feasibility study.

BACKGROUND: While guidelines for laparoscopic abdominal surgery advise using the lowest possible intra-abdominal pressure, commonly a standard pressure is used. We evaluated the feasibility of a predefined multifaceted individualized pneumoperitoneum strategy aiming at the lowest possible intra-abdominal pressure during laparoscopic colorectal surgery. METHODS: Multicenter prospective study in patients scheduled for laparoscopic colorectal surgery. The strategy consisted of ventilation with low tidal volume, a modified lithotomy position, deep neuromuscular blockade, pre-stretching of the abdominal wall, and individualized intra-abdominal pressure titration; the effect was blindly evaluated by the surgeon. The primary endpoint was the proportion of surgical procedures completed at each individualized intra-abdominal pressure level. Secondary endpoints were the respiratory system driving pressure, and the estimated volume of insufflated CO2 gas needed to perform the surgical procedure. RESULTS: Ninety-two patients were enrolled in the study. Fourteen cases were converted to open surgery for reasons not related to the strategy. The intervention was feasible in all patients and well-accepted by all surgeons. In 61 out of 78 patients (78%), surgery was performed and completed at the lowest possible IAP, 8 mmHg. In 17 patients, IAP was raised up to 12 mmHg. The relationship between IAP and driving pressure was almost linear. The mean estimated intra-abdominal CO2 volume at which surgery was performed was 3.2 L. CONCLUSION: A multifaceted individualized pneumoperitoneum strategy during laparoscopic colorectal surgery was feasible and resulted in an adequate working space in most patients at lower intra-abdominal pressure and lower respiratory driving pressure. ClinicalTrials.gov (Trial Identifier: NCT03000465).

Influence of tetanic stimulation on the staircase phenomenon and the acceleromyographic time-course of neuromuscular block: a randomized controlled trial.

During neuromuscular monitoring, repeated electrical stimulation evokes muscle responses of increasing magnitude ('staircase phenomenon', SP). We aimed to evaluate whether SP affects time course and twitches' values of an acceleromyographic assessed neuromuscular block with or without previous tetanic stimulation. Fifty adult patients were randomized to receive a 50 Hz tetanic stimulus (S group) or not (C group) before monitor calibration. After 20 min of TOF ratio (TOFr) stimulation rocuronium was administered. Onset time of block (primary endpoint), recovery of T1 to 25%, TOFr to 0.9, and recovery index were compared. We also compared T1 and TOFr at baseline, post-stimulation, and during recovery from block. Moreover the correlation between T1 at maximum recovery and (a) baseline T1 and (b) post-stimulation T1 along with T1/TOFr ratio during recovery were evaluated. After stimulation median T1 increased (32%) in group C and decreased (16%) in group S (P = 0.0001). Onset time (Median [IQR] in seconds) was 90 (29-77) vs. 75 (28-60) in C and S group (P = 0.002). Time [Mean (SD) in minutes] to normalized TOFr 0.9 were 70.13 (14.9) vs. 62.1 (21.2) in C and S groups (P = 0.204). TOFr showed no differences between groups at any time point. T1 at maximum recovery showed a stronger correlation with post-stabilization T1 compared to baseline. (ρ = 0.80 and ρ = 0.85, for C and S groups.) Standard calibration does not ensure twitch baseline stabilization and prolongs onset time of neuromuscular block. TOF ratio is not influenced by SP.

Underneath Images and Robots, Looking Deeper into the Pneumoperitoneum: A Narrative Review.

Laparoscopy offers numerous advantages over open procedures, minimizing trauma, reducing pain, accelerating recovery, and shortening hospital stays. Despite other technical advancements, pneumoperitoneum insufflation has received little attention, barely evolving since its inception. We explore the impact of pneumoperitoneum on patient outcomes and advocate for a minimally invasive approach that prioritizes peritoneal homeostasis. The nonlinear relationship between intra-abdominal pressure (IAP) and intra-abdominal volume (IAV) is discussed, emphasizing IAP titration to balance physiological effects and surgical workspace. Maintaining IAP below 10 mmHg is generally recommended, but factors such as patient positioning and surgical complexity must be considered. The depth of neuromuscular blockade (NMB) is explored as another variable affecting laparoscopic conditions. While deep NMB appears favorable for surgical stillness, achieving a balance between IAP and NMB depth is crucial. Temperature and humidity management during pneumoperitoneum are crucial for patient safety and optical field quality. Despite the debate over the significance of temperature drop, humidification and the warming of insufflated gas offer benefits in peritoneal homeostasis and visual clarity. In conclusion, there is potential for a paradigm shift in pneumoperitoneum management, with dynamic IAP adjustments and careful control of insufflated gas temperature and humidity to preserve peritoneal homeostasis and improve patient outcomes in minimally invasive surgery.

Impact of Standard Versus Low Pneumoperitoneum Pressure on Peritoneal Environment in Laparoscopic Cholecystectomy. Randomized Clinical Trial.

BACKGROUND: High CO 2 pneumoperitoneum pressure during laparoscopy adversely affects the peritoneal environment. This study hypothesized that low pneumoperitoneum pressure may be linked to less peritoneal damage and possibly to better clinical outcomes. MATERIALS AND METHODS: One hundred patients undergoing scheduled laparoscopic cholecystectomy were randomized 1:1 to low or to standard pneumoperitoneum pressure. Peritoneal biopsies were performed at baseline time and 1 hour after peritoneum insufflation in all patients. The primary outcome was peritoneal remodeling biomarkers and apoptotic index. Secondary outcomes included biomarker differences at the studied times and some clinical variables such as length of hospital stay, and quality and safety issues related to the procedure. RESULTS: Peritoneal IL6 after 1 hour of surgery was significantly higher in the standard than in the low-pressure group (4.26±1.34 vs. 3.24±1.21; P =0.001). On the contrary, levels of connective tissue growth factor and plasminogen activator inhibitor-I were higher in the low-pressure group (0.89±0.61 vs. 0.61±0.84; P =0.025, and 0.74±0.89 vs. 0.24±1.15; P =0.028, respectively). Regarding apoptotic index, similar levels were found in both groups and were 44.0±10.9 and 42.5±17.8 in low and standard pressure groups, respectively. None of the secondary outcomes showed differences between the 2 groups. CONCLUSIONS: Peritoneal inflammation after laparoscopic cholecystectomy is higher when surgery is performed under standard pressure. Adhesion formation seems to be less in this group. The majority of patients undergoing surgery under low pressure were operated under optimal workspace conditions, regardless of the surgeon's expertise.

Low intra-abdominal pressure in laparoscopic surgery: a systematic review and meta-analysis.

BACKGROUND: Guidelines do not provide clear recommendations with regard to the use of low intra-abdominal pressure (IAP) during laparoscopic surgery. The aim of this meta-analysis is to assess the influence of low versus standard IAP during laparoscopic surgery on the key-outcomes in perioperative medicine as defined by the StEP-COMPAC consensus group. MATERIALS AND METHODS: We searched the Cochrane Library, PubMed, and EMBASE for randomized controlled trials comparing low IAP (<10 mmHg) with standard IAP (10 mmHg or higher) during laparoscopic surgery without time, language, or blinding restrictions. According to the PRISMA guidelines, two review authors independently identified trials and extracted data. Risk ratio (RR), and mean difference (MD), with 95% CIs were calculated using random-effects models with RevMan5. Main outcomes were based on StEP-COMPAC recommendations, and included postoperative complications, postoperative pain, postoperative nausea and vomiting (PONV) scores, and length of hospital stay. RESULTS: Eighty-five studies in a wide range of laparoscopic procedures (7349 patients) were included in this meta-analysis. The available evidence indicates that the use of low IAP (<10 mmHg) leads to a lower incidence of mild (Clavien-Dindo grade 1-2) postoperative complications (RR=0.68, 95% CI: 0.53-0.86), lower pain scores (MD=-0.68, 95% CI: -0.82 to 0.54) and PONV incidence (RR=0.67, 95% CI: 0.51-0.88), and a reduced length of hospital stay (MD=-0.29, 95% CI: -0.46 to 0.11). Low IAP did not increase the risk of intraoperative complications (RR=1.15, 95% CI: 0.77-1.73). CONCLUSIONS: Given the established safety and the reduced incidence of mild postoperative complications, lower pain scores, reduced incidence of PONV, and shorter length of stay, the available evidence supports a moderate to strong recommendation (1a level of evidence) in favor of low IAP during laparoscopic surgery.

Risk Factors for One-Year Mortality in Hospitalized Adults with Severe COVID-19.

As the body's immunity declines with age, elderly-hospitalized patients due to COVID-19 might be at higher mortality risk. Therefore, the aim of this prospective study was to examine the possible risk factors (demographic, social or comorbidities) most associated with mortality one-year after diagnosis of COVID-19. Routine data were collected from a cohort of hospitalized adults with severe COVID-19. The primary endpoint was mortality at one-year after diagnosis of COVID-19. We used a Cox proportional hazard model to estimate the hazard ratios (HRs) for both all-cause and specific cardiorespiratory mortality. A fully adjusted model included sex, socioeconomic status, institutionalization status, disability, smoking habit, and comorbidities as confounders. A total of 368 severe cases hospitalized on average 67.3 ± 15.9 years old were included. Participants aged ≥ 71 years had significantly higher HRs for all-cause mortality (adjusted HRs = 2.86, 95%CI: 2.01-4.07) and cardiorespiratory mortality (adjusted HRs = 2.86, 95%CI: 1.99-4.12). The association between age and mortality after diagnosis of COVID-19 due to both all-causes and cardiorespiratory mortality showed a consistent dose-response fashion. Institutionalization, disability, and socioeconomic status also showed a significant association with mortality. In conclusion, aging itself was the most important risk factor associated with mortality one year after diagnosis of COVID-19. People with disabilities, institutionalized or low socioeconomic status are significantly more likely to die after COVID-19.

Solid Tumor Opioid Receptor Expression and Oncologic Outcomes: Analysis of the Cancer Genome Atlas and Genotype Tissue Expression Project.

Background: Opioid receptors are expressed not only by neural cells in the central nervous system, but also by many solid tumor cancer cells. Whether perioperative opioids given for analgesia after tumor resection surgery might inadvertently activate tumor cells, promoting recurrence or metastasis, remains controversial. We analysed large public gene repositories of solid tumors to investigate differences in opioid receptor expression between normal and tumor tissues and their association with long-term oncologic outcomes. Methods: We investigated the normalized gene expression of µ, κ, δ opioid receptors (MOR, KOR, DOR), Opioid Growth Factor (OGFR), and Toll-Like 4 (TLR4) receptors in normal and tumor samples from twelve solid tumor types. We carried out mixed multivariable logistic and Cox regression analysis on whether there was an association between these receptors' gene expression and the tissue where found, i.e., tumor or normal tissue. We also evaluated the association between tumor opioid receptor gene expression and patient disease-free interval (DFI) and overall survival (OS). Results: We retrieved 8,780 tissue samples, 5,852 from tumor and 2,928 from normal tissue, of which 2,252 were from the Genotype Tissue Expression Project (GTEx) and 672 from the Cancer Genome Atlas (TCGA) repository. The Odds Ratio (OR) [95%CI] for gene expression of the specific opioid receptors in the examined tumors varied: MOR: 0.74 [0.63-0.87], KOR: 1.27 [1.17-1.37], DOR: 1.66 [1.48-1.87], TLR4: 0.29 [0.26-0.32], OGFR: 2.39 [2.05-2.78]. After controlling all confounding variables, including age and cancer stage, there was no association between tumor opioid receptor expression and long-term oncologic outcomes. Conclusion: Opioid receptor gene expression varies between different solid tumor types. There was no association between tumor opioid receptor expression and recurrence. Understanding the significance of opioid receptor expression on tumor cells remains elusive.

Opioid Receptor Expression in Colorectal Cancer: A Nested Matched Case-Control Study.

Background: There is growing interest in the possible effect of perioperative anesthetic management on the growth and spread of cancer. The impact of perioperative use of opioids on cancer recurrence remains controversial and an assessment cannot yet be established based on current publications. This study aimed to assess the differential expression of opioid receptors between healthy and tumor tissues in patients with stage II and III colorectal cancer undergoing elective surgery by immunohistochemistry (IHC). Methods: Propensity-score matched case-control study nested in a retrospective cohort of patients with stage II or III colorectal. The primary endpoint was the difference in µ-opioid receptor (MOR) expression measured by IHC between tumor and healthy tissue in subject with or without recurrence. Secondary endpoints were to evaluate the differences in Opioid Growth Factor Receptor (OGFR), cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) in the matched sample and from a from samples of colorectal cancer stored in the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression Project (GTEx). Results: There was a significant difference in MOR receptor (median 3 [intequartile range IQR: 1-3] and 0 [IQR: 0-2], P<0.001) and OGFR receptor (median 6 [IQR: 5-6] and 2 [IQR: 1-2], P<0.001) in tumor and control tissue respectively. However, there were no significant differences in cAMP nor PKA expression between both types of tissues and in expression in any of the analyzed variables by recurrence status. The MOR and OGFR expression data from TCGA database were similar to our sample size data with lower expression of MOR and higher expression of OGFR in tumoural samples with a skewed distribution for MOR expression in tumor tissue both in patients with and without recurrence. Conclusion: In patients with stage II and III colorectal cancer, overall expression of MOR and OGFR was significantly increased but was not different between previously matched patients with or without recurrence. No differences were found in the analyzed metabolic pathway of cAMP-PKA: These results were confirmed by an in silico analysis of samples from the TCGA-GTEx database.