Randomized clinical trial of fluid and salt restriction compared with a controlled liberal regimen in elective gastrointestinal surgery.

BACKGROUND: Excessive intravenous fluid prescription may play a causal role in postoperative complications following major gastrointestinal resectional surgery. The aim of this study was to investigate whether fluid and salt restriction would decrease postoperative complications compared with a more modern controlled liberal regimen. METHODS: In this observer-blinded single-site randomized clinical trial consecutive patients undergoing major gastrointestinal resectional surgery were randomized to receive either a liberal control fluid regimen or a restricted fluid and salt regimen. The primary outcome was postoperative complications of grade II and above (moderate to severe). RESULTS: Some 240 patients (194 colorectal resections and 46 oesophagogastric resections) were enrolled in the study; 121 patients were randomized to the restricted regimen and 119 to the control (liberal) regimen. During surgery the control group received a median (interquartile range) fluid volume of 2033 (1576-2500) ml and sodium input of 282 (213-339) mmol, compared with 1000 (690-1500) ml and 142 (93-218) mmol respectively in the restricted group. There was no significant difference in major complication rate between groups (38·0 and 39·0 per cent respectively). Median (range) hospital stay was 8 (3-101) days in the controls and 8 (range 3-76) days among those who received restricted fluids. There were four in-hospital deaths in the control group and two in the restricted group. Substantial differences in weight change, serum sodium, osmolality and urine : serum osmolality ratio were observed between the groups. CONCLUSION: There were no significant differences in major complication rates, length of stay and in-hospital deaths when fluid restriction was used compared with a more liberal regimen. REGISTRATION NUMBER: ISRCTN39295230 (http://www.controlled-trials.com).

Management of gallstone pancreatitis: effects of deviation from clinical guidelines.

CONTEXT: Recently published management guidelines for acute pancreatitis provide a standard against which practice can be measured. Specifically it is recommended all patients with gallstone induced pancreatitis have definitive clearance of gallstones within four weeks. OBJECTIVE: To determine if practice in our institution followed these guidelines and to analyse the effects of delayed clearance of gallstones. METHODS: Seventy-six consecutive patients with gallstone pancreatitis presenting within a 15 month period were prospectively studied to compare management with national guidelines and to determine rates of recurrent biliary-pancreatic disease due to delay in clearance of gallstones. RESULTS: Only 5 of 76 patients (6.6%) had operative removal of gallstones within four weeks of their episode of acute pancreatitis. Only 34 of 76 patients (44.7%) had their gallstones removed during the follow up period (minimum 8 months). Fourteen of 76 patients (18.4%) had unplanned readmissions to hospital with biliary-pancreatic disease, necessitating a total of 135 days in hospital. CONCLUSIONS: It is clear from this study that guidelines for the management of gallstone acute pancreatitis are not being met, resulting in high rates of readmission with related disease.

Investigation of the interleukin 1 gene cluster and its association with acute pancreatitis.

The interleukin 1 (IL-1) gene cluster has been implicated in acute pancreatitis. Penta-allelic and bi-allelic polymorphisms exist in the IL-1RN and IL-1B genes, respectively. The aim of the study was to investigate these polymorphisms in acute pancreatitis. Genotype and allele frequencies were determined in patients (n = 116) and healthy controls (n = 170) using the polymerase chain reaction. PCR products from the IL-1B study were further digested with Taq I restriction endonuclease. Patients were categorised according to aetiology, severity, and organ-failure scores. Allele 1 of the IL-1RN polymorphism was significantly increased in patients compared with controls (72.0 vs. 63.0%; p = 0.029, Pc = 0.029), in severe cases compared with controls (81.9 vs. 63.0%; p = 0.002, Pc = 0.004), in idiopathics compared with controls (82.4 vs. 63.0%; p = 0.002, Pc = 0.006), and in severe cases compared with mild cases (81.9 vs. 67.5%; p = 0.023, Pc = 0.046). Allele 2 was significantly decreased in severe cases compared with controls (18.1 vs. 33.0%; p = 0.013, Pc = 0.026), in idiopathics compared with controls (17.6 vs. 33%; p = 0.013, Pc = 0.039), and in severe cases compared with mild cases (18.1 vs. 32.5%; p = 0.023, Pc = 0.046). No significant differences were found for the Taq I allele or genotype frequencies between controls and patients/subgroups of patients. IL-1RN appears to determine severity of acute pancreatitis and susceptibility to idiopathic acute pancreatitis. No association was found between IL-1B and the disease.

Cytokine gene polymorphisms in acute pancreatitis.

CONTEXT: Pro-inflammatory and regulatory cytokines play a key role in the pathogenesis of acute pancreatitis. Genetic loci encoding cytokines have been shown to be polymorphic, in some cases influencing protein expression. OBJECTIVE: To investigate if TNF and IL-10 gene loci are associated with the occurrence or severity of acute pancreatitis. SETTING: Acute surgical unit within large district hospital serving a population of 500,000. METHODS, Three TNF microsatellite loci (TNFa, TNFb, TNFc), the TNF-308 polymorphism, the IL-10.G microsatellite locus, and 3 i-allelic polymorphisms in the IL-10 5' region were typed using PCR in 135 acute pancreatitis patients and ethnically matched normal controls (n=107). Aetiology of disease was determined and patients grouped according to disease severity by assigning an organ failure score or classification according to the Atlanta system. MAIN OUTCOME MEASURES: Allelic frequency of polymorphic loci in patients with different aetiology and disease course in acute pancreatitis. RESULTS: No difference was noted in allelic frequency of any of the cytokine gene loci between groups stratified according to disease severity. When aetiology was studied again there was no significant difference in allelic frequency. CONCLUSIONS: The cytokine gene polymorphisms studied play no part in determination of disease severity or susceptibility to acute pancreatitis.

Acute pancreatitis: an overview of emerging pharmacotherapy.

Biotechnology has enabled greater understanding of the cellular and molecular biology of acute pancreatitis and has offered the possibility of a new generation of biodrugs to treat this disease. The proteases inhibitor gabexate mesilate has proven to be effective for endoscopic retrograde cholangiopancreatography-induced pancreatitis but, given the low incidence of this condition, its cost-effectiveness has to be evaluated. Randomised controlled trials have shown no benefit for somatostatin or its analogue octreotide although some practitioners continue to use it to prevent organ damage and complicated disease. Antioxidant therapy has been thoroughly investigated in animal models but the results of large scale clinical trials are awaited. The use of kinin inhibitors is in its infancy and has not yet reached the clinic. Considerable interest has been engendered in nitric oxide (NO), firstly for its beneficial use in acute lung injury resulting from the multi-organ failure of acute pancreatitis and secondly, the possible benefits of NOS inhibition to prevent pancreatitic necrosis. Tumour necrosis factor antagonism and interleukin- 1 blockade are 2 therapies awaiting clinical trials because there is overwhelming evidence of their benefit in animal models. Interleukin-10, an anticytokine, may have similar benefits and has been shown to be beneficial in animal models when given as pretreatment. The only biodrug that has progressed to phase III clinical trials is the platelet-activating factor antagonist lexipafant. Successful phase II studies have been followed up by a phase III study indicating benefits in reduction of organ failure and pseudocyst formation and reduction in mortality when treatment is given within 48 hours of onset of the disease. Finally, prophylactic therapy with selected antibacterials in patients with predicted severe disease can reduce local complications and possibly mortality.