Long-term outcome after early repair of iatrogenic bile duct injury. A national Danish multicentre study.

BACKGROUND: The aim of this retrospective study was to evaluate the peri-operative and long-term outcome after early repair with a hepaticojejunostomy (HJ). METHODS: Between 1995 and 2010, a nationwide, retrospective multi-centre study was conducted. All iatrogenic bile duct injury (BDI) sustained during a cholecystectomy and repaired with HJ in the five Hepato-Pancreatico-Biliary centres in Denmark were included. RESULTS: In total, 139 patients had an HJ repair. The median time from the BDI to reconstruction was 5 days. A concomitant vascular injury was identified in 26 cases (19%). Post-operative morbidity was 36% and mortality was 4%. Forty-two patients (30%) had a stricture of the HJ. The median follow-up time without stricture was 102 months. Nineteen out of the 42 patients with post-reconstruction biliary strictures had a re-HJ. Twenty-three patients were managed with percutaneous transhepatic cholangiography and dilation. The overall success rate of re-establishing the biliodigestive flow approached 93%. No association was found between timing of repair, concomitant vascular injury, level of injury and stricture formation. CONCLUSION: In this national, unselected and consecutive cohort of patients with BDI repaired by early HJ we found a considerable risk of long-term complications (e.g. 30% stricture rate) and mortality in both the short- and the long-term perspective.

Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease.

BACKGROUND & AIMS: Previous studies have shown conflicting results regarding the course of inflammatory bowel disease (IBD) after liver transplantation in patients with primary sclerosing cholangitis (PSC). We studied the progression of IBD in patients with PSC who have undergone liver transplantation. We also studied risk factors, including medical therapy, that could influence on IBD disease activity. METHODS: In a longitudinal multicenter study, we analyzed data from the Nordic Liver Transplant Group on 439 patients with PSC who underwent liver transplantation from November 1984 through December 2006; 353 had IBD at the time of transplantation. We compared IBD activity before and after liver transplantation. Two hundred eighteen patients who had an intact colon and had undergone pretransplant and post-transplant colonoscopies were characterized further. RESULTS: Macroscopic colonic inflammation was more frequent after liver transplantation than before liver transplantation (153 vs 124 patients; P < .001). The degree of inflammation decreased in 37 patients (17%), was unchanged in 93 patients (43%), and increased in 88 patients (40%) (P < .001). The rate of relapse after transplantation was higher than that before transplantation (P < .001), and overall clinical IBD activity also increased (P < .001). Young age at diagnosis of IBD and dual treatment with tacrolimus and mycophenolate mofetil were significant risk factors for increased IBD activity after transplantation, whereas combination treatment with cyclosporin A and azathioprine had protective effects. CONCLUSIONS: Immunosuppression affects IBD activity after liver transplantation in patients with PSC; a shift from present standard maintenance treatment of tacrolimus and mycophenolate mofetil to cyclosporin A and azathioprine should be considered for these patients.

Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation: a Nordic multicenter study.

OBJECTIVE: Several studies have implicated primary sclerosing cholangitis (PSC) as an additional risk factor for colorectal neoplasia in inflammatory bowel disease (IBD). Some reports have indicated that the risk is even higher in PSC-IBD patients after liver transplantation (Ltx), but this issue is controversial. We aimed to compare the risk of colorectal neoplasia in PSC-IBD patients before and after Ltx and to identify risk factors for colorectal neoplasia post-transplant. MATERIAL AND METHODS: In a multicenter study within the Nordic Liver Transplant Group, we assessed the risk of colorectal neoplasia by using the competing risk regression analysis. RESULTS: Among the 439 PSC patients included, 353 (80%) had IBD at the time of Ltx and 15 (3%) patients developed de novo IBD post-Ltx. The median duration of IBD was 15 (0-50) years at the time of Ltx and follow-up after Ltx was 5 (0-20) years. Ninety-one (25%) PSC-IBD patients developed colorectal neoplasia. The cumulative risk of colorectal neoplasia was higher after than before Ltx (HR: 1.9, 95% CI: 1.3-2.9, p = 0.002). A multivariate analysis demonstrated aminosalicylates and ursodeoxycholic acid as significantly associated with an increased risk of colorectal neoplasia post-Ltx. Duration and activity of IBD did not significantly affect the risk of neoplasia. CONCLUSION: The even higher risk of colorectal neoplasia in PSC-IBD patients after when compared with that of before Ltx underscores the importance of regular surveillance colonoscopies post-Ltx. The association of aminosalicylates and ursodeoxycholic acid to the development of colorectal neoplasia after Ltx should be further investigated.

Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy.

AIM: The objective of this systematic review and meta-analysis was to assess the efficacy of probiotics and synbiotics in patients with hepatic encephalopathy. METHODS: Eligible trials were identified by searching electronic databases including MEDLINE, the Cochrane Library, Science Citation Index and Embase, abstract proceedings, reference lists and ongoing trial registers until 13 October 2010. We included randomized controlled trials comparing probiotics and synbiotics with no intervention, placebo or lactulose in patients with hepatic encephalopathy. The primary outcome measure was improvement in hepatic encephalopathy. RESULTS were expressed as risk rates (RR) with confidence intervals (CI) and intertrial heterogeneity as I(2) . RESULTS: Seven trials with a total of 393 patients were analyzed. Compared to placebo or lactulose, treatment with probiotics or synbiotics significantly improved hepatic encephalopathy (RR = 1.40, 95% CI = 1.05-1.86, I(2) = 5%). Probiotics decreased arterial ammonia (weighted mean difference 15.95; 95% CI = 26.72-3.28; I(2) = 68%), but not venous ammonia (weighted mean difference 5.23; 95% CI = 21.77-11.30; I(2) = 89%). Treatment with probiotics or synbiotics did not significantly affect the psychometric tests. Overall adverse events were reported in four trials with no difference between probiotics and placebo groups (RR = 0.32, 95% CI = 0.04-2.57; I(2) = 59%). Regression analysis showed evidence of small-study effects. CONCLUSION: The present meta-analysis suggests that probiotics may be an effective treatment of hepatic encephalopathy, though rigorous evaluation in standardized, randomized, clinical trial with clinically relevant outcomes is still needed.

Pathophysiology and clinical implications of peroperative fluid management in elective surgery.

The purpose of this thesis was to describe pathophysiological aspects of perioperative fluid administration and create a rational background for future, clinical outcome studies. In laparoscopic cholecystectomy, we have found "liberal" crystalloid administration ( approximately 3 liters) to improve perioperative physiology and clinical outcome, which has implication for fluid management in other laparoscopic procedures such as laparoscopic fundoplication, laparoscopic repair of ventral hernia, hysterectomy etc., where 2-3 liters crystalloid should be administered based on the present evidence. That equal amounts of fluid caused adverse physiologic effects in healthy volunteers indicates that addition of the surgical trauma per se increases fluid requirements. Volume kinetic analysis applied 4 hours postoperatively was not able to detect the presence of either overhydration or hypovolemia regardless of the administered fluid volume intraoperatively. In knee arthroplasty a approximately 4 vs. approximately 2 liters crystalloid-based fluid regimen lead to significant hypercoagulability (although with unknown clinical implications), but no over-all differences in functional recovery. Dehydration caused by bowel preparation leads to functional hypovolemia and the deficits should be corrected, in particular in elderly patients, where preoperative intravenous fluid substitution of approximately 2-3 liters crystalloid is recommended. We did not find thoracic epidural anesthesia to be accompanied by intravascular fluid mobilization. In major (colonic) surgery with a standardized multimodal rehabilitation regimen, over-all functional recovery was not affected with a "liberal" ( approximately 5 liters) vs. "restrictive" 1.5 liter crystalloid-based regimen, however based on three anastomotic leakages in the "restrictive" group, it may be hypothesized that a too "restrictive" fluid administration strategy could be detrimental in patients with anastomoses and need further evaluation. A systematic review concluded that present evidence does not allow final recommendations on which type of fluid to administer in elective surgery. Based on the current evidence, administration of < 5 liters intravenous fluid without specific indication in major surgical procedures should be avoided, while administration of < 1.5 liters in patients with anastomoses may not be recommended, an issue needing clarification in large-scale clinical studies. Finally, we have demonstrated that the conduction of double-blinded randomized trials on fluid management with postoperative outcomes is feasible.

Reconstruction of major bile duct injuries after laparoscopic cholecystectomy.

INTRODUCTION: Bile duct injury (BDI) after cholecystectomy remains a serious complication with major implications for patient outcome. For most major BDIs, the recommended method of repair is a hepaticojejunostomy (HJ). We conducted a retrospective review aiming to examine the perioperative and the long-term outcome after reconstructive HJ at our institution. MATERIAL AND METHODS: Retrospective review of 41 consecutive patients with BDI sustained during cholecystectomy and subsequently managed with a HJ. The patients were referred to a tertiary hepato-biliary centre during a 15-year period (1994-2008). RESULTS: A total of 32 cases (78%) were reconstructed within two weeks of injury. While 14 patients (34%) suffered perioperative complications, 22 patients (54%) had a complication-free short as well as long-term outcome. Within a median follow-up period of 9.2 years, ten patients (24%) developed biliary strictures requiring percutaneous dilatation and/or further surgery. Three patients had further segmental hepatectomies and one patient developed secondary biliary cirrhosis necessitating orthotopic liver transplantation. No association was found between timing of repair or level of injury and outcome. CONCLUSION: Early specialist repair may result in acceptable short as well as long-term outcome; however, the morbidity of reconstructive biliary surgery remains high--particularly in the context of patient expectations before laparoscopic cholecystectomy.

[Systemic prokinetic treatment of postoperative ileus following abdominal surgery. Assessment of a Cochrane review]. / Systemisk prokinetisk behandling af postoperativ ileus efter abdominalkirurgi. Gennemgang af et Cochrane-review.

Based on the evidence presented in the Cochrane review "Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults", routine administration of systemic prokinetics for the prevention of postoperative ileus is not recommendable. The potential of selective opioid antagonists and intravenous lidocaine should be further investigated, particularly in conjunction with laparoscopic surgery, epidural pain management and fast-track surgery.

[Perioperative fluid therapy in perforated ulcers]. / Perioperativ vaeskebehandling ved perforeret ulcus.

INTRODUCTION: Surgery for perforated ulcers is one of the most common emergency surgical procedures. Approximately 400 procedures are performed each year in Denmark and mortality is high, reaching close to 30% at 30 days postoperatively. The importance of perioperative fluid administration during the perioperative course remains unclear. The purpose of this study is to describe the perioperative fluid management in these patients in order to identify problem areas (if any) and to create a basis on which future trials on fluid management in this patient group may be designed. MATERIAL AND METHODS: Retrospective survey of 45 consecutive patients operated for perforated ulcers over a 3-year period between 1 January 2003 and 31 December 2005 in the surgical department of a university hospital. RESULTS: Data that would permit rational fluid therapy are not being collected on a regular basis. Fluid balance charts were kept for 42 patients on the day of operation (89%), for 29 patients on the first post-operative day (61%), for 17 patients on the second post-operative day (36%) and for 12 patients (25%) on the third post-operative day. No patients were weighed for assessment of fluid status. Perioperative fluid administration varied extensively, with fluid balance on the day of surgery ranging from -45 to 8,030 ml (median 2688 ml) and a cumulated fluid balance of 7,2 litres (1,875-14,565 ml) three days postoperatively. Generally, patients had no fluid administered prior to surgery (median 0 ml, applying to 41 patients (87%) range 0-4,500 ml). CONCLUSION: Both the preoperative fluid management and the postoperative monitoring of the fluid balance are suboptimal and should be optimized. Individualized (goal-directed) fluid administration aiming at optimizing the oxygen supply to the peripheral tissues is warranted and is recommended to high-risk emergency surgery patients.

[Perioperative fluid therapy--what new?]. / Perioperativ vaeskebehandling--hvad nyt?

Limited evidence on perioperative fluid management has resulted in large variability in administered fluid regimens with unknown implications for the outcome. Present data indicate fluid overload and hypovolemia to be equally deleterious, and individualized fluid therapy may be recommended in high-risk patients undergoing major elective surgery. Future studies should be procedure-specific and with standardized perioperative management with increased focus on the postoperative period.

Liberal versus restrictive fluid management in knee arthroplasty: a randomized, double-blind study.

BACKGROUND: There are few data describing the relationship between amount of perioperative fluid and organ function. In this study we investigated the effects of two levels of intravascular fluid administration ("liberal" versus "restrictive") in knee arthroplasty on physiological recovery as the primary outcome variable. METHODS: In a double-blind study, 48 ASA I-III patients undergoing fast-track elective knee arthroplasty were randomized to restrictive or liberal perioperative intravascular fluid administration. Patients received a fixed rate infusion of Ringer's lactate solution with a standardized volume of colloid. All other aspects of perioperative management (including anesthesia, preoperative fluid status, and postoperative management) were standardized. Primary outcome variables included pulmonary function (spirometry), exercise capacity ("timed up and go" test), coagulation (Thrombelastograph), postoperative hypoxemia (nocturnal pulse oximetry), postoperative ileus (defecation), and subjective patient recovery (visual analog scales). Hospital stay and complications were also noted. RESULTS: Fluid guidelines were followed strictly in all patients. Liberal (median 4250 mL, range 3150-5200 mL) compared with restrictive (median 1740 mL, range 1100-2165 mL) intravascular fluid administration led to improved pulmonary function 6 h postoperatively, significant hypercoagulability 24-48 h postoperatively, and reduced incidence of vomiting. There were no overall differences in the other assessed perioperative physiological recovery variables (postoperative hypoxemia, exercise capacity or subjective patient recovery variables). No difference was found in hospital stay (median 4 days in both groups, not significant). CONCLUSION: A liberal compared to a restrictive intravascular fluid regimen may lead to significant hypercoagulability and a reduction in vomiting, but without differences in other recovery variables or hospital stay after fast-track knee arthroplasty.

Influence of "liberal" versus "restrictive" intraoperative fluid administration on elimination of a postoperative fluid load.

BACKGROUND: Previously, the authors found "liberal" fluid administration (approximately 3 l Ringer's lactate [RL]) to improve early rehabilitation after laparoscopic cholecystectomy, suggesting functional hypovolemia to be present in patients receiving "restrictive" fluid administration (approximately 1 l RL). Because volume kinetic analysis after a volume load may distinguish between hypovolemic versus normovolemic states, the authors applied volume kinetic analysis after laparoscopic cholecystectomy to explain the difference in outcome between 3 and 1 l RL. METHODS: In a prospective, nonrandomized trial, the authors studied 20 patients undergoing laparoscopic cholecystectomy. Ten patients received 15 ml/kg RL (group 1) and 10 patients received 40 ml/kg RL (group 2) intraoperatively. All other aspects of perioperative management were standardized. A 12.5-ml/kg RL volume load was infused preoperatively and 4 h postoperatively. The distribution and elimination of the fluid load was estimated using volume kinetic analysis. RESULTS: Patient baseline demographics and intraoperative data did not differ between groups, except for intraoperative RL, having a median of 1,118 ml (range, 900-1,400 ml) in group 1 compared with a median of 2,960 ml (range, 2,000-3,960 ml) in group 2 (P<0.01). There were no significant preoperative versus postoperative differences in the size of the body fluid space expanded by infused fluid (V), whereas the clearance constant kr was higher postoperatively versus preoperatively (P=0.03). The preoperative versus postoperative changes in volume kinetics including V were not different between the two groups. CONCLUSIONS: Elimination of an intravenous fluid load was increased after laparoscopic cholecystectomy per se but not influenced by the amount of intraoperative fluid administration.

[Penetrated IUD as the cause of stricture in the sigmoid colon]. / Penetreret kobber T-spiral som årsag til striktur i colon sigmoideum.

A 42-year-old woman became pregnant for the second and third times following insertion of an IUD in the puerperium of her first pregnancy. The IUD was thought to have been expelled. Nineteen years after insertion, the woman developed abdominal pain and diarrhoea. A sigmoid stricture was diagnosed by endoscopy. Laparotomy showed that the IUD had perforated the uterus and penetrated the sigmoid colon. Resection was performed. This case demonstrates the need to investigate every case of a missing IUD.

Treatment of anastomotic leakage after rectal resection with transrectal vacuum-assisted drainage (VAC). A method for rapid control of pelvic sepsis and healing.

OBJECTIVE: Anastomotic leakage after rectal resection is associated with high morbidity and mortality. Patients without peritonitis can be treated conservatively by transrectal rinsing and drainage. However, healing is often very slow, and formation of abundant scar tissue resulting in a poor functional result is not uncommon. Vacuum-assisted closure (VAC) has been shown to accelerate wound healing by increasing local blood flow, reducing bacterial load and stimulating growth of granulation tissue. In this paper, we describe VAC as a method for treating anastomotic leakage after rectal resection. METHODS: Four patients with anastomotic leakage after rectal resections were treated with VAC. RESULTS: Healing time for these patients was median 51 days (43-195). The control group consisted of patients treated conservatively in the previous 5-year period. Ten patients were identified with median healing time 336 days (52-1434). CONCLUSION: VAC treatment may possibly shorten healing time of anastomotic leakages after rectal resection. However, the presented results are preliminary, with only few patients included, and obviously, larger, randomized, clinical trials are needed to confirm these results and establish the indication for VAC treatment in clinical practice. We believe VAC therapy is a promising treatment of anastomotic leakage after rectal resection.

Liberal versus restrictive fluid administration to improve recovery after laparoscopic cholecystectomy: a randomized, double-blind study.

OBJECTIVE: The objective of this study was to investigate the effects of 2 levels of intraoperative fluid administration on perioperative physiology and outcome after laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: Intraoperative fluid administration is variable as a result of limited knowledge of physiological and clinical effects of different fluid substitution regimens. METHODS: In a double-blind study, 48 ASA I-II patients undergoing laparoscopic cholecystectomy were randomized to 15 mL/kg (group 1) or 40 mL/kg (group 2) intraoperative administration of lactated Ringer's solution (LR). All other aspects of perioperative management as well as preoperative fluid status were standardized. Primary outcome parameters were assessed repeatedly for the first 24 postoperative hours and included pulmonary function (spirometry), exercise capacity (submaximal treadmill test), cardiovascular hormonal responses, balance function, pain, nausea and vomiting, recovery, and hospital stay. RESULTS: Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR led to significant improvements in postoperative pulmonary function and exercise capacity and a reduced stress response (aldosterone, antidiuretic hormone, and angiotensin II). Nausea, general well-being, thirst, dizziness, drowsiness, fatigue, and balance function were also significantly improved, as well as significantly more patients fulfilled discharge criteria and were discharged on the day of surgery with the high-volume fluid substitution. CONCLUSIONS: Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR improves postoperative organ functions and recovery and shortens hospital stay after laparoscopic cholecystectomy.

Physiologic effects of bowel preparation.

PURPOSE: Despite the universal use of bowel preparation before colonoscopy and colorectal surgery, the physiologic effects have not been described in a standardized setting. This study was designed to investigate the physiologic effects of bowel preparation. METHODS: In a prospective study, 12 healthy volunteers (median age, 63 years) underwent bowel preparation with bisacodyl and sodium phosphate. Fluid and food intake were standardized according to weight, providing adequate calorie and oral fluid intake. Before and after bowel preparation, weight, exercise capacity, orthostatic tolerance, plasma and extracellular volume, balance function, and biochemical parameters were measured. RESULTS: Bowel preparation led to a significant decrease in exercise capacity (median, 9 percent) and weight (median, 1.2 kg). Plasma osmolality was significantly increased from 287 to 290 mmol kg(-1), as well as increased phosphate and urea concentrations, whereas calcium and potassium concentrations decreased significantly after bowel preparation. No differences in plasma or extracellular volumes were seen. Orthostatic tolerance and balance function did not change after bowel preparation. CONCLUSIONS: Bowel preparation has significant adverse physiologic effects, which may be attributed to dehydration. The majority of these findings is small and may not be of clinical relevance in otherwise healthy patients undergoing bowel preparation and following recommendations for oral fluid intake.

Bupivacaine in microcapsules prolongs analgesia after subcutaneous infiltration in humans: a dose-finding study.

In this study, we examined the onset and duration of local analgesic effects of bupivacaine incorporated into biodegradable microcapsules (extended-duration local anesthetic; EDLA) administered as subcutaneous infiltrations in different doses in humans. In 18 volunteers, the skin on the medial calf was infiltrated with 10 mL of EDLA, and the opposite calf was infiltrated with 10 mL of aqueous bupivacaine (5.0 mg/mL) in a double-blinded, randomized manner. Three different concentrations of EDLA were tested (6.25, 12.5, and 25 mg/mL), with 6 subjects in each group. Pain responses to mechanical and heat stimuli and sensory thresholds (touch, warm, and cold detection thresholds) were examined by von Frey hairs and contact thermodes. Assessments were made before and 2, 4, 6, 8, 24, 48, 72, 96, and 168 h after the injections. Safety evaluations were performed daily for the first week and at 2 wk, 6 wk, and 6 mo after the injections. The time to maximum effects was significantly shorter for aqueous bupivacaine (2-6 h) than for EDLA (4-24 h), but there were no significant differences between the maximum effects of EDLA and aqueous bupivacaine. From 24 to 96 h after the injections, EDLA was significantly more efficient than aqueous bupivacaine for all variables, and significant effects of EDLA were demonstrated for at least 96 h for all variables. In general, a dose-response gradient was seen in the EDLA group for 5 of 7 variables when the curves expressing effect over time for the different concentrations were evaluated. No serious side effects were observed for up to 6 mo after administration. In conclusion, bupivacaine incorporated in microcapsules provided analgesia for 96 h after subcutaneous infiltration.

Thiopental and propofol affect different regions of the brain at similar pharmacologic effects.

Propofol has a greater amnesic effect than thiopental. In this study we tested whether different brain regions were affected by propofol and thiopental at similar drug effects. Changes in regional cerebral blood flow (rCBF) were identified by using SPM99 analysis of images obtained with positron emission tomography with (15)O water. Ten right-handed male volunteers (age, 35 +/- 10 yr; weight, 74.1 +/- 7.5 kg; mean +/- sd) were randomized to receive thiopental (n = 4) or propofol (n = 6) to target sedative and hypnotic concentrations with bispectral index (BIS) monitoring. Four positron emission tomography images were obtained during various tasks at baseline and with sedative and hypnotic effects. Two participants receiving propofol were unresponsive at sedative concentrations and were not included in the final analyses. Median serum concentrations were 1.2 and 2.7 microg/mL for sedative and hypnotic propofol effects, respectively. Similarly, thiopental concentrations were 4.8 and 10.6 microg/mL. BIS decreased similarly in both groups. The pattern of rCBF change was markedly different for propofol and thiopental. Propofol decreased rCBF in the anterior (right-sided during sedation) brain regions, whereas thiopental decreased rCBF primarily in the cerebellar and posterior brain regions. At similar levels of drug effect, propofol and thiopental affect different regions of the brain. These differences may help to identify the loci of action for the nonsedative effects of propofol, such as amnesia.