Trough anti-Xa activity after intermediate dose nadroparin for thrombosis prophylaxis in critically ill patients with COVID-19 and acute kidney injury.

Our objective was to assess the incidence of drug bioaccumulation in critically ill COVID-19 patients with AKI receiving intermediate dose nadroparin for thrombosis prophylaxis. We conducted a Prospective cohort study of critically ill COVID-19 patients. In patients on intermediate dose nadroparin (5700 IU once daily) we assessed the incidence of bioaccumulation (trough anti-Xa level > 0.2 IU/mL) stratified according to presence of AKI. We quantified this association using multilevel analyses. To assess robustness of our observations, we explored the association between AKI and anti-Xa activity in patients receiving high dose nadroparin (> 5700 IU). 108 patients received intermediate dose nadroparin, of whom 24 had AKI during 36 anti-Xa measurements. One patient with AKI (4.2% [95%CI 0.1-21%]) and 1 without (1.2% [95%CI 0.03-6.5%]) developed bioaccumulation (p = 0.39). Development of AKI was associated with a mean increase of 0.04 (95%CI 0.02-0.05) IU/ml anti-Xa activity. There was no statistically significant association between anti-Xa activity and AKI in 51 patients on high dose nadroparin. There were four major bleeding events, all in patients on high dose nadroparin. In conclusion, Bioaccumulation of an intermediate dose nadroparin did not occur to a significant extent in critically ill patients with COVID-19 complicated by AKI. Dose adjustment in AKI may be unnecessary.

Plexus anesthesia versus general anesthesia for carotid endarterectomy: A systematic review with meta-analyses.

INTRODUCTION: Traditional carotid endarterectomy is considered to be the standard technique for prevention of a new stroke in patients with a symptomatic carotid stenosis. Use of plexus anesthesia or general anesthesia in traditional carotid endarterectomy is, to date, not unequivocally proven to be superior to one other. A systematic review was needed for evaluation of benefits and harms to determine which technique, plexus anesthesia or general anesthesia is more effective for traditional carotid endarterectomy in patients with symptomatic carotid stenosis. METHODS: The review was conducted according to our protocol following the recommendations of Cochrane and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Searches were updated on the October 1, 2020. We did not find any randomized clinical trial comparing plexus anesthesia and general anesthesia in carotid endarterectomy with patch angioplasty matching our protocol criteria in patients with a symptomatic and significant (≥50%) carotid stenosis. CONCLUSIONS: Based on the current, high risk of bias evidence, we concluded there is a need for new randomized clinical trials with overall low risk of bias comparing plexus anesthesia with general anesthesia in carotid endarterectomy with patch closure of the arterial wall in patients with a symptomatic and significant (≥50%) stenosis of the internal carotid artery.Protocol unique identification number (UIN): CRD42019139913, (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=139913).

Plexus anesthesia versus general anesthesia in patients for carotid endarterectomy with patch angioplasty: Protocol for a systematic review with meta-analyses and Trial Sequential Analysis of randomized clinical trials.

INTRODUCTION: Traditional carotid endarterectomy is considered to be the standard technique for prevention of a new stroke in patients with a symptomatic carotid stenosis. Use of plexus anesthesia or general anesthesia in traditional carotid endarterectomy is, to date, not unequivocally proven to be superior to one other. A systematic review is needed for evaluation of benefits and harms to determine which technique, plexus anesthesia or general anesthesia is more effective for traditional carotid endarterectomy in patients with symptomatic carotid stenosis. METHODS AND OUTCOMES: The review will be conducted according to this protocol following the recommendations of the 'Cochrane Handbook for Systematic Reviews' and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Randomized Clinical Trials comparing plexus anesthesia versus general anesthesia in traditional carotid endarterectomy will be included. Primary outcomes will be postoperative death and/ or stroke (<30 days) and serious adverse events. Secondary outcomes will be non-serious adverse events.We will primarily base our conclusions on meta-analyses of trials with overall low risk of bias. We will use Trial Sequential Analysis to assist the evaluation of imprecision in Grading of Recommendations Assessment, Development and Evaluation. However, if pooled point-estimates of all trials are similar to pooled point-estimates of trials with overall low risk of bias and there is lack of a statistical significant interaction between estimates from trials with overall high risk of bias and trials with overall low risk of bias we will consider the Trial Sequential Analysis adjusted confidence interval precision of the estimate achieved in all trials as the result of our meta-analyses. ETHICS AND DISSEMINATION: The proposed systematic review will collect and analyze secondary data from already performed studies therefore ethical approval is not required. The results of the systematic review will be disseminated by publication in a peer-review journal and submitted for presentation at relevant conferences.

Timing of onset of gastrointestinal bleeding in the ICU: Protocol for a preplanned observational study.

BACKGROUND: Critically ill patients are at risk of gastrointestinal bleeding, but clinically important gastrointestinal bleeding is rare. The majority of intensive care unit (ICU) patients receive stress ulcer prophylaxis (SUP), despite uncertainty concerning the balance between benefit and harm. For approximately half of ICU patients with gastrointestinal bleeding, onset is early, ie within the first two days of the ICU stay. The aetiology of gastrointestinal bleeding and consequently the balance between benefit and harm of SUP may differ between patients with early vs late gastrointestinal bleeding. METHODS: This is a protocol and statistical analysis plan for a preplanned exploratory substudy of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) randomized clinical trial, comparing intravenous pantoprazole (40 mg once daily) with placebo in 3350 acutely ill adult ICU patients. We will describe baseline characteristics and assess the time to onset of the first clinically important episode of GI bleeding accounting for survival status and allocation to SUP or placebo. In addition, we will describe differences in therapeutic and diagnostic procedures used in patients with clinically important gastrointestinal bleeding according to early vs late bleeding and 90-day vital status. CONCLUSIONS: The study outlined in this protocol will provide detailed information on patient characteristics and the timing of onset of gastrointestinal bleeding in the patients enrolled in the SUP-ICU trial. This may provide additional knowledge and incentives for future studies on which patients benefit from SUP.

Systematic overview and critical appraisal of meta-analyses of interventions in intensive care medicine.

RATIONALE: Meta-analysed intervention effect estimates are perceived to represent the highest level of evidence. However, such effects and the randomized clinical trials which are included in them need critical appraisal before the effects can be trusted. OBJECTIVE: Critical appraisal of a predefined set of all meta-analyses on interventions in intensive care medicine to assess their quality and assessed the risks of bias in those meta-analyses having the best quality. METHODS: We conducted a systematic search to select all meta-analyses of randomized clinical trials on interventions used in intensive care medicine. Selected meta-analyses were critically appraised for basic scientific criteria, (1) presence of an available protocol, (2) report of a full search strategy, and (3) use of any bias risk assessment of included trials. All meta-analyses which qualified these criteria were scrutinized by full "Risk of Bias in Systematic Reviews" ROBIS evaluation of 4 domains of risks of bias, and a "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" PRISMA evaluation. RESULTS: We identified 467 meta-analyses. A total of 56 meta-analyses complied with these basic scientific criteria. We scrutinized the risks of bias in the 56 meta-analyses by full ROBIS evaluation and a PRISMA evaluation. Only 4 meta-analyses scored low risk of bias in all the 4 ROBIS domains and 41 meta-analyses reported all 27 items of the PRISMA checklist. CONCLUSION: In contrast with what might be perceived as the highest level of evidence only 0.9% of all meta-analyses were judged to have overall low risk of bias.

Stress ulcer prophylaxis in the intensive care unit trial: detailed statistical analysis plan.

BACKGROUND: In this statistical analysis plan, we aim to provide details of the pre-defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. The aim of the SUP-ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU). METHODS: The SUP-ICU trial is an investigator-initiated, international, multicentre, randomised, blinded, parallel-group trial of intravenously pantoprazole 40 mg once daily vs. placebo in 3350 acutely ill adult ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support, serious adverse reactions, 1-year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre-defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables comparing the two intervention groups in the intention-to-treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention-to-treat population. CONCLUSION: Stress ulcer prophylaxis is standard of care in ICUs worldwide, but has never been tested in large high-quality randomised placebo-controlled trials. The SUP-ICU trial will provide important high-quality data on the balance between the benefits and harms of stress ulcer prophylaxis in adult critically ill patients.

Incidence, timing and outcome of AKI in critically ill patients varies with the definition used and the addition of urine output criteria.

BACKGROUND: Acute kidney injury (AKI) is a serious complication of critical illness with both attributed morbidity and mortality at short-term and long-term. The incidence of AKI reported in critically ill patients varies substantially with the population evaluated and the definitions used. We aimed to assess which of the AKI definitions (RIFLE, AKIN or KDIGO) with or without urine output criteria recognizes AKI most frequently and quickest. Additionally, we conducted a review on the comparison of incidence proportions of varying AKI definitions in populations of critically ill patients. METHODS: We included all patients with index admissions to our intensive care unit (ICU) from January 1st, 2014 until June 11th, 2014 to determine the incidence and onset of AKI by RIFLE, AKIN and KDIGO during the first 7 days of ICU admission. We conducted a sensitive search using PubMed evaluating the comparison of RIFLE, AKIN and KDIGO in critically ill patients RESULTS: AKI incidence proportions were 15, 21 and 20% respectively using serum creatinine criteria of RIFLE, AKIN and KDIGO. Adding urine output criteria increased AKI incidence proportions to 35, 38 and 38% using RIFLE, AKIN and KDIGO definitions. Urine output criteria detected AKI in patients without AKI at ICU admission in a median of 13 h (IQR 7-22 h; using RIFLE definition) after admission compared to a median of 24 h using serum creatinine criteria (IQR24-48 h). In the literature a large heterogeneity exists in patients included, AKI definition used, reference or baseline serum creatinine used, and whether urine output in the staging of AKI is used. CONCLUSION: AKIN and KDIGO criteria detect more patients with AKI compared to RIFLE criteria. Addition of urine output criteria detect patients with AKI 11 h earlier than serum creatinine criteria and may double AKI incidences in critically ill patients. This could explain the large heterogeneity observed in literature.

Glucocorticosteroids for sepsis: systematic review with meta-analysis and trial sequential analysis.

INTRODUCTION: Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light on this clinically important question. METHODS: A systematic review was conducted according to a published protocol and The Cochrane Handbook methodology including meta-analyses, TSA of randomised clinical trials, and external validity estimation (GRADE). Randomised clinical trials evaluating steroids were included for sepsis patients (systemic inflammatory response syndrome, sepsis, severe sepsis or septic shock) aged >18 years. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/Medline, Embase, Web of Science and Cinahl were searched until 18 February 2015. No language restrictions were applied. Primary outcomes were mortality at longest follow-up and serious adverse events. RESULTS: A total of 35 trials randomising 4682 patients were assessed and reviewed in full text. All trials but two had high risk of bias. No statistically significant effect was found for any dose of steroids versus placebo or no intervention on mortality at maximal follow-up [relative risk (RR) 0.89; TSA adjusted confidence interval (CI) 0.74-1.08]. Two trials with low risk of bias also showed no statistically significant difference (random-effects model RR 0.38, 95% CI 0.06-2.42). Similar results were obtained in subgroups of trials stratified according to high (>500 mg) or low (≤ 500 mg) dose hydrocortisone (or equivalent) (RR 0.87; TSA-adjusted CI 0.38-1.99; and RR 0.90; TSA-adjusted CI 0.49-1.67, respectively). There were also no statistically significant effects on serious adverse events other than mortality (RR 1.02; TSA-adjusted CI 0.7-1.48). The effects did not vary according to the degree of sepsis. TSA showed that many more randomised patients are needed before definitive conclusions may be drawn. CONCLUSION: Evidence to support or negate the use of steroids in any dose in sepsis patients is lacking. The results of ongoing and future well-designed, large randomised clinical trials are needed.

Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries.

BACKGROUND: Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries. METHODS: Adult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups. RESULTS: Ninety-seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2-receptor antagonists were used 31% (30/97) of the units. Twenty-three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP. CONCLUSIONS: In this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications.

The totally extraperitoneal method versus Lichtenstein's technique for inguinal hernia repair: a systematic review with meta-analyses and trial sequential analyses of randomized clinical trials.

BACKGROUND: Lichtenstein's technique is considered the reference technique for inguinal hernia repair. Recent trials suggest that the totally extraperitoneal (TEP) technique may lead to reduced proportions of chronic pain. A systematic review evaluating the benefits and harms of the TEP compared with Lichtenstein's technique is needed. METHODOLOGY/PRINCIPAL FINDINGS: The review was performed according to the 'Cochrane Handbook for Systematic Reviews'. Searches were conducted until January 2012. Patients with primary uni- or bilateral inguinal hernias were included. Only trials randomising patients to TEP and Lichtenstein were included. Bias evaluation and trial sequential analysis (TSA) were performed. The error matrix was constructed to minimise the risk of systematic and random errors. Thirteen trials randomized 5404 patients. There was no significant effect of the TEP compared with the Lichtenstein on the number of patients with chronic pain in a random-effects model risk ratio (RR 0.80; 95% confidence interval (CI) 0.61 to 1.04; p = 0.09). There was also no significant effect on number of patients with recurrences in a random-effects model (RR 1.41; 95% CI 0.72 to 2.78; p = 0.32) and the TEP technique may or may not be associated with less severe adverse events (random-effects model RR 0.91; 95% CI 0.73 to 1.12; p = 0.37). TSA showed that the required information size was far from being reached for patient important outcomes. CONCLUSIONS/SIGNIFICANCE: TEP versus Lichtenstein for inguinal hernia repair has been evaluated by 13 trials with high risk of bias. The review with meta-analyses, TSA and error matrix approach shows no conclusive evidence of a difference between TEP and Lichtenstein on the primary outcomes chronic pain, recurrences, and severe adverse events.

TIPP and Lichtenstein modalities for inguinal hernia repair: a cost minimisation analysis alongside a randomised trial.

The transinguinal preperitoneal (TIPP) technique using a soft mesh with a memory ring was developed recently for inguinal hernia repair. To compare TIPP with the Lichtenstein method, a randomised trial was conducted (ISRCTN93798494). The aim of this study was to perform an economic evaluation of the TIPP modality compared to the Lichtenstein modality from both a hospital and societal perspective alongside the clinical trial. The TULIP study was a double-blind randomised clinical trial comparing two techniques for inguinal hernia repair (TIPP and Lichtenstein). Correct generation of the allocation sequence, allocation concealment, blinding, and follow-up were used/applied according to the recommendations of the Cochrane Handbook. Next to the cost drivers, the short-form-36 health survey (SF-36) data from the TULIP trial was used to determine utility. The SF-36 data from the TULIP trial were revised using the SF-6D algorithm according to Brazier. Two scenarios-a hospital and a societal perspective-were presented. If the analyses showed no difference in effects (on the SF-6D) the cost effectiveness decision rule to cost minimisation was altered. No significant difference in SF-6D utility between both modalities was found (mean difference: 0.888, 95% CI -1.02 to 1.23); consequently, the economic decision rule became cost minimisation. For the hospital perspective no significant differences in costs were found (mean difference: euro -13, 95% CI euro -130 to euro 104). However, when including productivity gains in the analysis, significant differences (P = 0.037) in costs favouring the TIPP modality (mean saving: euro 1,472, 95% CI euro 463- euro 2,714) were found. The results show that TIPP is a cost-saving inguinal hernia repair technique compared to the Lichtenstein modality against equal effectiveness expressed as quality adjusted life week at 1 year given a societal perspective. In the trial, TIPP patients showed on average a quicker recovery of 6.5 days compared to Lichtenstein patients.

Randomized clinical trial of chronic pain after the transinguinal preperitoneal technique compared with Lichtenstein's method for inguinal hernia repair.

BACKGROUND: Preliminary experience has suggested that preperitoneal mesh positioning causes less chronic pain than Lichtenstein's technique for inguinal hernia repair. Therefore, a randomized clinical trial was conducted with the aim of evaluating the incidence of postoperative chronic pain after transinguinal preperitoneal (TIPP) mesh repair versus Lichtenstein's technique. METHODS: Patients with a primary unilateral inguinal hernia were randomized to either TIPP or Lichtenstein's repair in two training hospitals. The primary outcome was the number of patients with chronic pain after surgery. Secondary outcomes were adverse events. Follow-up was scheduled after 14 days, 3 months and 1 year. Patients and outcome assessors were blinded. RESULTS: A total of 302 patients were randomized to TIPP (143) or Lichtenstein (159) repair. Baseline characteristics were comparable in the two groups. Some 98.0 per cent of the patients were included in the analysis (141 in the TIPP group and 155 in the Lichtenstein group). Significantly fewer patients in the TIPP group had continuous chronic pain 1 year after surgery: five patients (3.5 per cent) versus 20 patients (12.9 per cent) in the Lichtenstein group (P = 0.004). An additional 12 patients (8.5 per cent) in the TIPP group and 60 (38.7 per cent) in the Lichtenstein group experienced pain during activity (P = 0.001). There were two patients with recurrence in the TIPP group and four in the Lichtenstein group, but no significant differences were found in other severe adverse events between the groups. CONCLUSION: Fewer patients had continuous chronic pain at 1 year after the TIPP mesh inguinal hernia repair compared with Lichtenstein's repair.

The transrectus sheath preperitoneal mesh repair for inguinal hernia: technique, rationale, and results of the first 50 cases.

INTRODUCTION: Laparoscopic and endoscopic hernia repair popularized the preperitoneal mesh position due to promising results concerning less chronic pain. However, considerable proportions of severe adverse events, learning curves, or added costs have to be taken into account. Therefore, open preperitoneal mesh techniques may have more advantages. The open approach to the preperitoneal space (PPS) according to transrectus sheath preperitoneal (TREPP) mesh repair is through the sheath of the rectus abdominus muscle. This technique provides an excellent view of the PPS and facilitates elective or acute hernia reduction and mesh positioning under direct vision. In concordance with the promising transinguinal preperitoneal inguinal hernia repair experiences in the literature, we investigated the feasibility of TREPP. METHODS: A rationale description of the surgical technique, available level of evidence for thoughts behind technical considerations. Furthermore, a descriptive report of the clinical outcomes of our pilot case series including 50 patients undergoing the TREPP mesh repair. RESULTS: A consecutive group of our first 50 patients were operated with the TREPP technique. No technical problems were experienced during the development of this technique. No conversions to Lichtenstein repair were necessary. No recurrences and no chronic pain after a mean follow-up of 2 years were notable findings. CONCLUSION: This description of the technique shows that the TREPP mesh repair might be a promising method because of the complete preperitoneal view, the short learning curve, and the stay-away-from-the-nerves principle. The rationale of the TREPP repair is discussed in detail.

Robustness assessments are needed to reduce bias in meta-analyses that include zero-event randomized trials.

OBJECTIVES: Meta-analysis of randomized trials with binary data can use a variety of statistical methods. Zero-event trials may create analytic problems. We explored how different methods may impact inferences from meta-analyses containing zero-event trials. METHODS: Five levels of statistical methods are identified for meta-analysis with zero-event trials, leading to numerous data analyses. We used the binary outcomes from our Cochrane review of randomized trials of laparoscopic vs. small-incision cholecystectomy for patients with symptomatic cholecystolithiasis to illustrate the influence of statistical method on inference. RESULTS: In seven meta-analyses of seven outcomes from 15 trials, there were zero-event trials in 0 to 71.4% of the trials. We found inconsistency in significance in one of seven outcomes (14%; 95% confidence limit 0.4%-57.9%). There was also considerable variability in the confidence limits, the intervention-effect estimates, and heterogeneity for all outcomes. CONCLUSIONS: The statistical method may influence the inference drawn from a meta-analysis that includes zero-event trials. Robustness assessments are needed to reduce bias in meta-analyses that include zero-event trials.

Systematic review: open, small-incision or laparoscopic cholecystectomy for symptomatic cholecystolithiasis.

BACKGROUND: Laparoscopic cholecystectomy has become the method of choice for gallbladder removal, although evidence of superiority over open and small-incision cholecystectomy is lacking. AIM: To compare the effects of open, small-incision and laparoscopic cholecystectomy techniques for patients with symptomatic cholecystolithiasis. METHODS: We conducted updated searches until January 2007 in multiple databases. We assessed bias risk. RESULTS: Fifty-nine trials randomized 5556 patients. No significant differences in primary outcomes (mortality and complications) were found among all three techniques. Both minimal invasive techniques show advantages over open cholecystectomy in terms of convalescence. Small-incision cholecystectomy showed shorter operative time compared with laparoscopic cholecystectomy (random effects, weighted mean difference, 16.4 min; 95% confidence interval, 8.9-23.8), but the two techniques did not differ regarding hospital stay and conversions. CONCLUSIONS: No significant differences in mortality and complications were found among all three techniques. Laparoscopic cholecystectomy and small-incision cholecystectomy are preferred over open cholecystectomy for quicker convalescence. Laparoscopic cholecystectomy and small-incision cholecystectomy show no clear differences on patient outcomes.

Feasibility of right-sided total extraperitoneal procedure for inguinal hernia repair after appendectomy: a prospective cohort study.

BACKGROUND: Totally extraperitoneal (TEP) endoscopic hernia surgery is increasingly popular since it is associated with little postoperative pain and with early return to work. Previous appendectomy may preclude preperitoneal dissection in patients with right-sided hernias. The feasibility of TEP surgery in these patients was the subject of the present study. METHODS: Between January 2005 and February 2007 all consecutive patients undergoing TEP surgery were included in a prospective cohort study. The study group consisted of patients with right-sided and bilateral hernias. Operative times, conversions, complication rates, and return to daily activities were recorded. Patients were divided into two groups according to previous appendectomy. RESULTS: A total of 462 patients with right-sided hernias underwent TEP surgery: 421 patients without previous abdominal surgery (group 1) and 41 patients with previous appendectomy (group 2). The conversion rate was significantly higher in group 2: four patients (10%) were converted to open Lichtenstein repair versus five (1%) in group 1 (p = 0.005). However, we found no significant differences in complication rate, operative time, and return to daily activities. CONCLUSIONS: A right-sided (or bilateral) TEP procedure may be performed safely in patients after previous appendectomy. Despite a higher conversion rate, the vast majority of patients can be operated endoscopically.

Laparoscopic vs. small incision cholecystectomy: Implications for pulmonary function and pain. A randomized clinical trial.

BACKGROUND: Upper abdominal surgery, including laparoscopic cholecystectomy (LC), is associated with post-operative pulmonary dysfunction. LC has, by consensus, become the treatment of choice for symptomatic cholecystolithiasis. The small-incision cholecystectomy (SIC), a procedure which does not require a pneumoperitoneum threatens to be lost to clinical practice even though there is evidence of equality. We hypothesized that the SIC technique should be equal and might even be superior to the LC when considering post-operative pulmonary function due to the short incision length. METHODS: A single-centre, randomized clinical trial was performed including patients scheduled for elective cholecystectomy. Pulmonary flow-volume curves were measured pre-operatively, post-operatively, and at follow up. Blood gas analyses were measured pre-operative, in the recovery phase and on post-operative day 1. Anaesthesia, analgesics, and peri-operative care were standardized by protocol. Post-operatively, patients and caregivers were blinded to the procedure. RESULTS: A total of 257 patients were analysed. There was one pulmonary complication (pneumonia) in the LC group. In both groups, similar reductions of approximately 20% in pulmonary function parameters occurred, with complete recovery to pre-operative values. Patients in the SIC group consumed more analgesia when compared with the LC group without impact on blood gas analysis. Patients converted to a conventional open technique showed significant differences in six of the eight parameters in pulmonary function tests. CONCLUSION: When evaluated with strict methodology and standardization of care, no clinically relevant differences were found between SIC and LC regarding pulmonary function. Our results suggest that the popularity of the laparoscopic technique cannot be attributed to pulmonary preservation.

Anaesthesiological considerations in small-incision and laparoscopic cholecystectomy in symptomatic cholecystolithiasis: implications for pulmonary function. A randomized clinical trial.

BACKGROUND: Upper abdominal surgery, including laparoscopic cholecystectomy (LC), is associated with post-operative pulmonary dysfunction. LC has, by consensus, become the treatment of choice for symptomatic cholecystolithiasis. Small-incision cholecystectomy (SIC), a procedure that does not require a pneumoperitoneum, threatens to be lost to clinical practice, even though there is evidence of equality. We hypothesized that the SIC technique should be equal, and might even be superior, to LC when considering post-operative pulmonary function because of the short incision length. METHODS: A single-centre randomized clinical trial was performed including patients scheduled for elective cholecystectomy. Pulmonary flow-volume curves were measured pre-operatively, post-operatively and at follow-up. Blood gas analyses were measured pre-operatively, in the recovery phase and on post-operative day 1. Anaesthesia, analgesics and peri-operative care were standardized by protocol. Post-operatively, patients and caregivers were blind to the procedure. RESULTS: Two hundred and fifty-seven patients were analysed. There was one pulmonary complication (pneumonia) in the LC group. In both groups, similar reductions of approximately 20% in pulmonary function parameters occurred, with complete recovery to pre-operative values. Patients in the SIC group consumed more analgesia when compared with the LC group, without any impact on blood gas analysis. Patients converted to a conventional open technique showed significant differences in six of the eight parameters in pulmonary function tests. CONCLUSION: When evaluated with strict methodology and standardization of care, no clinically relevant differences were found between SIC and LC with regard to pulmonary function. Our results suggest that the popularity of the laparoscopic technique cannot be attributed to pulmonary preservation.

Gallstone disease: Surgical aspects of symptomatic cholecystolithiasis and acute cholecystitis.

Indications for cholecystectomy are limited to clearly symptomatic gallstones. Relatively high failure rates of pain relief are probably caused by incorrect selection of patients for the operation. Contraindications for (laparoscopic) cholecystectomy are related to anaesthesiological considerations. Laparoscopic cholecystectomy was accepted by consensus as the gold standard within 5 years of its introduction. Nevertheless, both the classical open and small-incision cholecystectomies are safe alternatives, and superiority of any one of the three techniques over the others has not been proven. Primary outcome measures (mortality, complications, and symptom relief) seem to be equal for the three techniques. Acute cholecystitis is a complication of gallstones. Generally it is recommended that early cholecystectomy be performed, as delayed cholecystectomy is associated with longer total hospital stay and convalescence due to recurrent cholecystitis episodes. Cholecystostomy is an alternative technique for patients unfit for general anaesthesia. Reported complication and conversion rates in cholecystectomy for acute cholecystitis vary, but are higher than for symptomatic cholecystolithiasis. New developments--such as robot-assisted surgery--are expected to have a significant impact in the near future.

Small-incision versus open cholecystectomy for patients with symptomatic cholecystolithiasis.

BACKGROUND: Cholecystectomy is one of the most frequently performed operations. Open cholecystectomy has been the gold standard for over 100 years. Small-incision cholecystectomy is a less frequently used alternative. OBJECTIVES: To compare the beneficial and harmful effects of small-incision versus open cholecystectomy for patients with symptomatic cholecystolithiasis. SEARCH STRATEGY: We searched TheCochrane Hepato-Biliary Group Controlled Trials Register (6 April 2004), The Cochrane Library (Issue 1, 2004), MEDLINE (1966 to January 2004), EMBASE (1980 to January 2004), Web of Science (1988 to January 2004), and CINAHL (1982 to January 2004) for randomised trials. SELECTION CRITERIA: All published and unpublished randomised trials in patients with symptomatic cholecystolithiasis comparing any kind of small-incision or other kind of minimal incision cholecystectomy versus any kind of open cholecystectomy. No language limitations were applied. DATA COLLECTION AND ANALYSIS: Two authors independently performed selection of trials and data extraction. The methodological quality of the generation of the allocation sequence, allocation concealment, blinding, and follow-up was evaluated to assess bias risk. Analyses were based on the intention-to-treat principle. Authors were requested additional information in case of missing data. Sensitivity and subgroup analyses were performed if appropriate. MAIN RESULTS: Seven trials randomised 571 patients. Bias risk was high in the included trials. No mortality was reported. The total complication proportions are respectively 9.9% and 9.3% in the small-incision and open group, which is not significantly different (risk difference all trials, random-effects 0.00, 95% confidence interval (CI) -0.06 to 0.07). There are also no significant differences considering severe complications and bile duct injuries. However, small-incision cholecystectomy has a shorter hospital stay (weighted mean difference, random-effects -2.8 days (95% CI -4.9 to -0.6)) compared to open cholecystectomy. AUTHORS' CONCLUSIONS: Small-incision and open cholecystectomy seem to be equivalent regarding risks of complications, but the latter method is associated with a significantly longer hospital stay. The quicker recovery of small-incision cholecystectomy compared with open cholecystectomy confirms the existing preference of this technique over open cholecystectomy.