Saurabh Jamdar

Pro/con debate: Antifungal prophylaxis is important to prevent fungal infection in patients with acute necrotizing pancreatitis receiving broad-spectrum antibiotics

When critically ill patients with pancreatitis develop infection of the pancreas, the ongoing management of such patients becomes difficult. Sufficient evidence supports the use of broad-spectrum antibiotic prophylaxis to prevent the development of bacterial infection. Since fungal infection is also a relatively common complication of severe pancreatitis – particularly when broad-spectrum antibiotics are used – it seems logical that fungal prophylaxis may be an important component of management. In this issue of Critical Care, two expert groups debate the merits of antifungal prophylaxis in patients with acute necrotizing pancreatitis who are receiving antibiotics.

Drotrecogin alfa (recombinant human activated protein C) in severe acute pancreatitis

IntroductionCurrent concepts of the pathophysiology of acute pancreatitis suggest that disease progression from acinar injury to systemic illness involves a complex interplay between cellular and soluble inflammatory mediators and endothelial beds. To date, there is no specific pharmacologic intervention for acute pancreatitis. Death from acute pancreatitis remains a major issue, and late deaths are often related to haemorrhage and are associated with unresolved intra-abdominal sepsis. Drotrecogin alfa, an analogue of endogenous protein C, has antithrombotic, anti-inflammatory and profibrinolytic properties, and it has been shown to reduce mortality in clinical sepsis. Modulation of the coagulation cascade, although probably essential to the mode of action of drotrecogin alfa, can lead to an increased risk of bleeding.ObjectiveThe findings of the PROWESS trial have led to a more widespread use of drotrecogin alfa in sepsis and, critically, in sepsis-related conditions. The present article provides a concise summary of the interaction between the pathophysiology of acute pancreatitis and the modes of action of drotrecogin alfa, placing particular emphasis on the risks related to haemorrhage. Attention is further drawn to the reports of use of drotrecogin alfa in severe acute pancreatitis.ConclusionSynthesis of current knowledge on the modes of action and the side-effect profiles of drotrecogin alfa into a practical management algorithm must accept that evidence in this field is changing rapidly. At present there is insufficient evidence to justify the use of drotrecogin alfa in the early stages of this disease. In the later stages, when the probability of infection is proportionately greater, it is probable that intensive care clinicians will turn to drotrecogin alfa, in particular, in the setting of recent-onset organ dysfunction in established severe acute pancreatitis. Although this can be justified by extrapolation of the evidence from the PROWESS trial, practical critical care management in this setting must not overlook the need to rule out infection of necrosis, and must further be cognisant of the specific risks of haemorrhage in patients with prolonged pancreatitis and pancreatic necrosis.

Contemporary management of infected necrosis complicating severe acute pancreatitis

Pancreatic necrosis complicating severe acute pancreatitis is a challenging scenario in contemporary critical care practice; it requires multidisciplinary care in a setting where there is a relatively limited evidence base to support decision making. This commentary provides a concise overview of current management of patients with infected necrosis, focusing on detection, the role of pharmacologic intervention, and the timing and nature of surgical interventions. Fine-needle aspiration of necrosis remains the mainstay for establishment of infection. Pharmacological intervention includes antibiotic therapy as an adjunct to surgical debridement/drainage and, more recently, drotrecogin alfa. Specific concerns remain regarding the suitability of drotrecogin alfa in this setting. Early surgical intervention is unhelpful; surgery is indicated when there is strong evidence for infection of necrotic tissue, with the current trend being toward less drastic surgical interventions.

Antibiotic use in acute pancreatitis: An audit of current practice in a tertiary centre.

INTRODUCTIONnIntravenous antibiotic prophylaxis is not recommended in acute pancreatitis. According to current international guidelines antibiotics together with further intervention should be considered in the setting of infected necrosis. Appropriate antibiotic therapy particularly avoiding over-prescription is important. This study examines antibiotic use in acute pancreatitis in a tertiary centre using the current IAP/APA guidelines for reference.nnnMETHODSnData were collected on a consecutive series of patients admitted with acute pancreatitis over a 12 month period. Data were dichotomized by patients admitted directly to the centre and tertiary transfers. Information was collected on clinical course with specific reference to antibiotic use, episode severity, intervention and outcome.nnnRESULTSn111 consecutive episodes of acute pancreatitis constitute the reported population. 31 (28%) were tertiary transfers. Overall 65 (58.5%) patients received antibiotics. Significantly more tertiary transfer patients received antibiotics. Mean person-days of antibiotic use was 23.9 (sd 29.7) days in the overall study group but there was significantly more use in the tertiary transfer group as compared to patients having their index admission to the centre (40.9 sd 37.1 vs 10.2 sd 8.9; Pxa0<xa00.005). Thirty four (44%) of patients with clinically mild acute pancreatitis received antibiotics.nnnCONCLUSIONSnThere is substantial use of antibiotics in acute pancreatitis, in particular in patients with severe disease. Over-use is seen in mild acute pancreatitis. Better consideration must be given to identification of prophylaxis or therapy as indication. In relation to repeated courses of antibiotics in severe disease there must be clear indications for use.

Outcomes following liver trauma in equestrian accidents.

BackgroundEquestrian sports are common outdoor activities that may carry a risk of liver injury. Due to the relative infrequency of equestrian accidents the injury patterns and outcomes associated with liver trauma in these patients have not been well characterized.MethodsWe examined our experience of the management of equestrian liver trauma in our regional hepatopancreaticobiliary unit at a tertiary referral center. The medical records of patients who sustained liver trauma secondary to equestrian activities were analysed for parameters such as demographic data, liver function tests, patterns of injury, radiological findings, the need for intervention and outcomes.Results20 patients sustained liver trauma after falling from or being kicked by a horse. The majority of patients were haemodynamically stable on admission. Alanine transaminase (ALT) levels were elevated in all patients and right-sided rib fractures were a frequently associated finding. CT demonstrated laceration of the liver in 12 patients, contusion in 3 and subcapsular haematoma in 2. The right lobe of the liver was most commonly affected. Only two patients required laparotomy and liver resection; the remaining 18 were successfully managed conservatively.ConclusionsThe risk of liver injury following a horse kick or falling off a horse should not be overlooked. Early CT imaging is advised in these patients, particularly in the presence of high ALT levels and concomitant chest injuries such as rib fractures. Despite significant liver trauma, conservative management in the form of close observation, ideally in a high-dependency setting, is often sufficient. Laparotomy is only rarely warranted and associated with a significantly higher risk of post-operative bile leaks.

Impact of portal vein embolization on long-term survival of patients with primarily unresectable colorectal liver metastases (Br J Surg 2010; 97: 240-250).

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Mis-use of antibiotics in acute pancreatitis: Insights from the United Kingdom's National Confidential Enquiry into patient outcome and death (NCEPOD) survey of acute pancreatitis

BACKGROUNDnInternational guidelines for the management of acute pancreatitis state that antibiotics should only be used to treat infectious complications. Antibiotic prophylaxis is not recommended. The aim of this study was to analyse antibiotic use, and its appropriateness, from a national review of acute pancreatitis.nnnMETHODSnData were collected from The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) study into the management of acute pancreatitis. Adult patients admitted to hospitals in England and Wales between January and June 2014 with a coded diagnosis of acute pancreatitis were included. Clinical and organisational questionnaires were used to collect data and these submissions subjected to peer review. Antibiotic use, including indication and duration were analysed.nnnRESULTSn439/712 (62%) patients received antibiotics, with 891 separate prescriptions and 23 clinical indications. A maximum of three courses of antibiotics were prescribed, with 41% (290/712) of patients receiving a second course and 24% (174/712) a third course. For the first antibiotic prescription, the most common indication was unspecified (85/439). The most common indication for the second course was sepsis (54/290), unspecified was the most common indication for the third course (50/174). In 72/374 (19.38%) the indication was deemed inappropriate by the clinicians and in 72/393 (18.3%) by case reviewers.nnnCONCLUSIONSnInappropriate use of antibiotics in acute pancreatitis is common. Healthcare providers should ensure that antimicrobial policies are in place as part of an antimicrobial stewardship process. This should include specific guidance on their use and these policies must be accessible, adherence audited and frequently reviewed.

Efficacy and safety of pharmacological venous thromboembolism prophylaxis following liver resection: a systematic review and meta-analysis

BACKGROUNDnCurrent guidelines recommend pharmacological prophylaxis for patients undergoing abdominal surgery for malignancy. Liver resection exposes patients to risk factors for venous thromboembolism, but there is a risk of bleeding. The aim of this study is to evaluate the evidence base supporting the use of pharmacological thromboprophylaxis in liver surgery.nnnMETHODSnAn electronic search was carried out for studies reporting the incidence of VTE following liver resection comparing patients receiving pharmacological prophylaxis with those who did not. The search resulted in 990 unique citations. Following the application of strict eligibility criteria 5 studies comprise the final study population.nnnRESULTSnIncluded studies report on 3675 patients undergoing liver resection between 1999 and 2013. 2256 patients received chemical thromboprophylaxis, 1412 had mechanical prophylaxis only and 7 received no prophylaxis. Meta-analysis revealed lower VTE rates in patients receiving chemical thromboprophylaxis (2.6%) compared to without prophylaxis (4.6%) (Dichotomous correlation test, odds ratio: 0.631 [95% Cl: 0.416-0.959], Fixed model, pxa0=xa00.030). Data regarding bleeding could not be pooled for meta-analysis, but chemical thromboprophylaxis was reported as safe in four studies.nnnCONCLUSIONnThis systematic review and meta-analysis of retrospective studies indicates that the use of perioperative chemical thromboprophylaxis reduces VTE incidence following liver surgery without an apparent increased risk of bleeding.

Colorectal Liver Metastases

Colorectal cancer can metastasize to the liver by three potential routes; the most common are via the portal venous drainage of the liver and the lymphatic drainage of the large intestine with a third mechanism being direct invasion of the liver by a tumor of the hepatic flexure [1].