Hubert A. Prins

Effect of a Comprehensive Surgical Safety System on Patient Outcomes

BACKGROUND Adverse events in patients who have undergone surgery constitute a large proportion of iatrogenic illnesses. Most surgical safety interventions have focused on the operating room. Since more than half of all surgical errors occur outside the operating room, it is likely that a more substantial improvement in outcomes can be achieved by targeting the entire surgical pathway. METHODS We examined the effects on patient outcomes of a comprehensive, multidisciplinary surgical safety checklist, including items such as medication, marking of the operative side, and use of postoperative instructions. The checklist was implemented in six hospitals with high standards of care. All complications occurring during admission were documented prospectively. We compared the rate of complications during a baseline period of 3 months with the rate during a 3-month period after implementation of the checklist, while accounting for potential confounders. Similar data were collected from a control group of five hospitals. RESULTS In a comparison of 3760 patients observed before implementation of the checklist with 3820 patients observed after implementation, the total number of complications per 100 patients decreased from 27.3 (95% confidence interval [CI], 25.9 to 28.7) to 16.7 (95% CI, 15.6 to 17.9), for an absolute risk reduction of 10.6 (95% CI, 8.7 to 12.4). The proportion of patients with one or more complications decreased from 15.4% to 10.6% (P<0.001). In-hospital mortality decreased from 1.5% (95% CI, 1.2 to 2.0) to 0.8% (95% CI, 0.6 to 1.1), for an absolute risk reduction of 0.7 percentage points (95% CI, 0.2 to 1.2). Outcomes did not change in the control hospitals. CONCLUSIONS Implementation of this comprehensive checklist was associated with a reduction in surgical complications and mortality in hospitals with a high standard of care. (Netherlands Trial Register number, NTR1943.).

Nature and timing of incidents intercepted by the SURPASS checklist in surgical patients

Introduction More than half of in-hospital adverse events can be attributed to a surgical discipline. Checklists can effectively decrease errors and adverse events. However, the mechanisms by which checklists lead to increased safety are unclear. This study aimed to assess the number, nature and timing of incidents intercepted by use of the Surgical Patient Safety System (SURPASS) checklist, a patient-specific multidisciplinary checklist that covers the entire surgical patient pathway. Methods The checklist was implemented in two academic hospitals and four teaching hospitals in the Netherlands. Users of the checklist had three options for each item that was checked: ‘not applicable’, ‘yes’ and ‘intercepted by checklist’. In each hospital, the first 1000 completed checklists were entered into an online central database. Results In six participating hospitals, 6313 checklists were collected. One or more incidents were intercepted in 2562 checklists (40.6%). In total, 6312 incidents were intercepted. After correction for the number of items and the extent of adherence in each part of the checklist, the number of intercepted incidents was highest in the preoperative and postoperative stages. Conclusions The checklist intercepts many potentially harmful incidents across all stages of the surgical patient pathway. The majority of incidents were intercepted in the preoperative and postoperative stages of the pathway. The degree to which these incidents would have been intercepted by a single checklist in the operating room only, compared with a checklist for the entire surgical pathway, remains a subject for future study.

The Long-term Results of a Randomized Clinical Trial of Laparoscopy-assisted Versus Open Surgery for Colon Cancer

Objective:The aim of this study was to compare the long-term outcome of laparoscopy-assisted colectomy (LAC) and open colectomy (OC) for nonmetastatic colon cancer. Methods:From November 1993 to July 1998 all patients with adenocarcinoma of the colon were assessed for entry in this single center, clinically randomized trial. Adjuvant therapy and postoperative follow-up were similar in both groups. The primary endpoint was cancer-related survival and secondary endpoints were probability of overall survival and probability of being free of recurrence. Data were analyzed according the intention-to-treat principle. Results:Two hundred and nineteen patients entered the study (111 LAC group and 108 OC group). The median follow-up was 95 months (range, 77–133). There was a tendency of higher cancer-related survival (P = 0.07, NS) and overall survival (P = 0.06, NS) for the LAC group. Probability of cancer-related survival was higher in the LAC group (P = 0.02) when compared with OC. The regression analysis showed that LAC was independently associated with a reduced risk of tumor relapse (hazard ratio 0.47, 95% CI 0.23–0.94), death from a cancer-related cause (0.44, 0.21–0.92) and death from any cause (0.59, 0.35–0.98). Conclusions:LAC is more effective than OC in the treatment of colon cancer.

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037)

BackgroundRecently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis).Methods/DesignIn this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmanns procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmanns procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs.DiscussionThe Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis.Trial registrationNederlands Trial Register NTR2037

Use of a mixture of medium-chain triglycerides and long-chaintriglycerides versus long-chain triglycerides in critically ill surgical patients: a randomized prospective double-blind study

Twenty critically-ill surgical patients who needed total parenteral nutrition were randomly enrolled in a double-blind study comparing two intravenous fat emulsions: one containing a mixture of 50% medium-chain triglycerides and 50% long-chain triglycerides and another containing 100% longchain triglycerides. The purpose of this study was to investigate metabolic and biochemical differences between both emulsions with special reference to liver enzymes. After a baseline period of 24 h with only glucose and NaCl infusion, the lipid emulsion was added continuously during 24 h over 5 days. The parenteral nutrition was administered in mixture bags containing amino-acids, glucose and lipids together. Two-thirds of the non-protein calories were administered as glucose 40% and one third as either long-chain triglycerides or a mixture of medium-chain triglycerides and long-chain triglycerides. The total amount of non-protein calories received was the measured energy expenditure during the baseline period plus 10% and was fixed during the study. Plasma substrate concentrations, energy expenditure, and nitrogen balance were determined and arterial blood samples were taken. No toxic effects or complications attributable to one of the two emulsions were observed. There was no significant difference in energy expenditure, nitrogen balance, liver function tests, carnitine, transferrin, pre-albumin, albumin, cholesterol, triglycerides and free fatty acids. The only parameter that showed a different pattern of reaction between the two emulsions was serum bilirubin concentration. In this study no evidence of any advantageous effect of a mixture of medium-chain triglycerides and long-chain triglycerides was seen.

Comparison of Short-Term Surgical Outcomes after Single-Incision Laparoscopic versus Multiport Laparoscopic Right Colectomy: A Two-Center, Prospective Case-Controlled Study of 100 Patients

Background: Recent case studies have demonstrated the feasibility of single-incision laparoscopic colectomy (SILC). Few comparative studies for SILC and multiport laparoscopic colectomy (MLC) have been conducted. The aim of this case-controlled study was to compare the short-term surgical outcomes between SILC and MLC for right-sided colectomies. Methods: Between January 2010 and February 2012, data from the first 50 consecutive patients that underwent right SILS at one of the two institutions were compared with a group of 50 consecutive patients that underwent right MLC in the same period. Results: Median operative time was significantly shorter in SILC (97 vs. 112 min; p < 0.001). Between both groups, no statistically significant differences were found regarding number and nature of short-term complications, number of reoperations [4 (8%) vs. 6 (12%)], and mortality rate [1 (2%) vs. 2 (4%)]. Median postoperative hospital stay was 6 days for both groups. Conclusion: SILC is a safe and feasible procedure when performed by experienced laparoscopic surgeons. Length of hospital stay and overall complication rates are comparable with MLC. Until today, no clear advantages of SILC over MLC have been demonstrated. However, due to its smaller incisional trauma, SILC could be a major step in improving cosmetic outcomes.

Elevation of asymmetric dimethylarginine (ADMA) in patients developing hepatic failure after major hepatectomy.

BACKGROUND Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the arginine-nitric oxide pathway. It is conceivable that its concentration is tightly regulated by urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver. In rats, we showed a high net hepatic uptake of ADMA. Therefore, we aimed to confirm the role of the liver in humans and hypothesized elevated ADMA levels after major liver resection by a reduction of functional liver mass and injury to the remnant liver. METHODS Patients undergoing a major hepatic resection (HEP, n = 17) or major abdominal surgery (MAS, n = 12) were included and followed in time. In addition, ADMA levels were measured in 4 patients having severe hepatic failure after a liver resection. Plasma ADMA concentration was measured by high-performance liquid chromatography. RESULTS Preoperatively and on days 1, 3, and 5, plasma levels of ADMA were higher in HEP patients when compared with MAS patients. In HEP patients with prolonged (>7 days) hepatic injury, ADMA levels were especially elevated. On the first postoperative day, ADMA significantly correlated to bilirubin concentration (r = .528, p < .05) as a marker of postoperative hepatic function. Besides, in patients with severe hepatic failure, ADMA levels were highly elevated. CONCLUSIONS In the present study, evidence was found for the role of the liver in the elimination of ADMA in humans. Increased levels of ADMA occur in the postoperative course after a major hepatic resection, especially when liver function is severely impaired. Further studies need to assess the role of ADMA in the development of complications after liver surgery.

Low arginine/asymmetric dimethylarginine ratio deteriorates systemic hemodynamics and organ blood flow in a rat model

Objective:Both arginine and asymmetric dimethylarginine (ADMA) play a crucial role in the arginine–nitric oxide pathway. Low arginine and high ADMA levels can be found in critically ill patients after major surgery. The aim of this study was to evaluate the effects of low arginine plasma concentrations in combination with high ADMA plasma concentrations on hemodynamics and organ blood flow. Design:Randomized, placebo-controlled animal laboratory investigation. Subjects:Male Wistar rats (n = 21), anesthetized. Interventions:Rats were randomly assigned to three groups: a control group, an ADMA group, or an arginase (ASE)/ADMA group. In the control group, rats received (at t = 0) an intravenous (IV) infusion of 1.5 mL 0.9% NaCl during a 20-minute period. After 60 minutes (t = 60), rats received an IV bolus of 1.0 mL 0.9% NaCl. In the ADMA group, rats received an IV infusion of 1.5 mL 0.9% NaCl during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). In the ASE/ADMA group, rats received an IV infusion of 1.5 mL ASE (3200 IU) solution during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). Measurements and Main Results:Infusion of ADMA (20 mg/kg) and ASE (3200 IU) resulted in increased plasma ADMA levels and decreased arginine levels. During the whole experiment, systemic hemodynamics (heart rate, mean arterial pressure [MAP], and cardiac output) were measured. In addition, organ blood flow was measured at t = 90 and t = 180 minutes, using fluorescent microspheres. Compared with the control group, MAP and systemic vascular resistance were increased after infusion of ADMA. Infusion of ASE in combination with ADMA significantly deteriorated systemic hemodynamics (MAP, cardiac output, stroke volume, and systemic vascular resistance) and organ blood flow through the kidney and spleen. In addition, an initial decrease in arterial flow, followed by a later major increase, and panlobular apoptosis and necrosis of the liver was observed. Conclusions:The current study shows that low arginine plasma levels in combination with high ADMA plasma levels deteriorates systemic hemodynamics and reduces blood flow through the kidney and spleen and liver. These data suggest that a diminished nitric oxide production may be involved in the onset of organ failure.

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial)

BackgroundWith the availability of infliximab, nowadays recurrent Crohns disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohns disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohns disease of the distal ileum with respect to quality of life and costs.Methods/designThe study is designed as a multicenter randomized clinical trial including patients with Crohns disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007.DiscussionThe LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohns disease.Trial registrationNederlands Trial Register NTR1150

Arginase release from red blood cells: possible link in transfusion induced immune suppression?

Arginine stimulates lymphocyte function and is degraded by arginase, an enzyme that is abundantly present in red blood cells. Arginase impairs lymphocyte function and responses in vitro. Leakage of arginase from stored red blood cells may be involved in the lymphocyte dysfunction associated in allogenic blood transfusion. In the present study, arginase activity was determined in bags of red cells stored for transfusion. Buffy coat depleted red blood cells were obtained routinely from four healthy donors and stored in bags for a maximum period of five weeks at 4 degrees C. The bags were sampled for determination of arginase, lactate dehydrogenase, and potassium. In addition, a random sample of 36 bags of red blood cells about to be transfused to patients were studied. Levels of arginase, lactate dehydrogenase, and potassium showed a time dependent increase in the bags of the four donors. This time dependent increase in arginase activity could be confirmed in the additional bags sampled (P < 0.0001, r = 0.78). The results for the first time show that arginase is released from red blood cells during storage for transfusion. Arginase infusion may play an important role in the immune suppression observed after blood transfusion.