A role for prophylactic antibiotics in necrotizing pancreatitis? Why we may never know the answer ...

The use of prophylactic antibiotics in patients with severe acute pancreatitis remains an intensely debated topic. Although animal studies consistently demonstrated an advantage of antibiotic prophylaxis, the only two blinded randomized controlled trials could not confirm these findings. Translation of the experimental models in human clinical practice is hampered by a number of fundamental differences between experimental pancreatitis and human disease, and therefore it is highly unlikely that the pronounced benefit found in experimental pancreatitis will ever be demonstrated in human disease. Early and accurate risk stratification to identify the patient at risk for infection early in the course of the disease seems to be the greatest challenge. Until we are able to demonstrate an advantage of antibiotic prophylaxis in a high-risk human population, the absence of proven benefit and potential side effects of this strategy should be acknowledged and the use of antibiotics should be limited to the treatment of documented infection

Is intra-abdominal hypertension a missing factor that drives multiple organ dysfunction syndrome?

In a recent issue of Critical Care, Cheng and colleagues conducted a rabbit model study that demonstrated that intra-abdominal hypertension (IAH) may damage both gut anatomy and function. With only 6 hours of IAH at 25 mmHg, these authors observed an 80% reduction in mucosal blood flow, an exponential increase in mucosal permeability, and erosion and necrosis of the jejunal villi. Such dramatic findings should remind all caring for the critically ill that IAH may severely damage the normal gut barrier functions and thus may be reasonably expected to facilitate bacterial and mediator translocation. The potential contribution of IAH as a confounding factor in the efficacy of selective decontamination of the digestive tract should be considered

Decompressive laparotomy for abdominal compartment syndrome – a critical analysis

INTRODUCTION: Abdominal compartment syndrome (ACS) is increasingly recognized in critically ill patients, and the deleterious effects of increased intraabdominal pressure (IAP) are well documented. Surgical decompression through a midline laparotomy or decompressive laparotomy remains the sole definite therapy for ACS, but the effect of decompressive laparotomy has not been studied in large patient series. METHODS: We reviewed English literature from 1972 to 2004 for studies reporting the effects of decompressive laparotomy in patients with ACS. The effect of decompressive laparotomy on IAP, patient outcome and physiology were analysed. RESULTS: Eighteen studies including 250 patients who underwent decompressive laparotomy could be included in the analysis. IAP was significantly lower after decompression (15.5 mmHg versus 34.6 mmHg before, p < 0.001), but intraabdominal hypertension persisted in the majority of the patients. Mortality in the whole group was 49.2% (123/250). The effect of decompressive laparotomy on organ function was not uniform, and in some studies no effect on organ function was found. Increased PaO(2)/FIO(2 )ratio (PaO(2 )= partial pressure of oxygen in arterial blood, FiO(2 )= fraction of inspired oxygen) and urinary output were the most pronounced effects of decompressive laparotomy. CONCLUSION: The effects of decompressive laparotomy have been poorly investigated, and only a small number of studies report its effect on parameters of organ function. Although IAP is consistently lower after decompression, mortality remains considerable. Recuperation of organ dysfunction after decompressive laparotomy for ACS is variable

Awareness and knowledge of intra-abdominal hypertension and abdominal compartment syndrome: results of an international survey

Background: Surveys have demonstrated a lack of physician awareness of intra-abdominal hypertension and abdominal compartment syndrome (IAH/ACS) and wide variations in the management of these conditions, with many intensive care units (ICUs) reporting that they do not measure intra-abdominal pressure (IAP). We sought to determine the association between publication of the 2006/2007 World Society of the Abdominal Compartment Syndrome (WSACS) Consensus Definitions and Guidelines and IAH/ACS clinical awareness and management. Methods: The WSACS Executive Committee created an interactive online survey with 53 questions, accessible from November 2006 until December 2008. The survey was endorsed by the WSACS, the European Society of Intensive Care Medicine (ESICM) and the Society of Critical Care Medicine (SCCM). A link to the survey was emailed to all members of the supporting societies. Participants of the 3rd World Congress on Abdominal Compartment Syndrome meeting (March 2007, Antwerp, Belgium) were also asked to complete the questionnaire. No reminders were sent. Based on 13 knowledge questions, an overall score was calculated (expressed as percentage). Results: A total of 2,244 of the approximately 10,000 clinicians who were sent the survey responded (response rate: 22.4%). Most of the 2,244 respondents (79.2%) completing the survey were physicians or physicians in training and the majority were residing in North America (53.0%). The majority of responders (85%) were familiar with IAP/IAH/ACS, but only 28% were aware of the WSACS consensus definitions for IAH/ACS. Three quarters of respondents considered the cut-off for IAH to be at least 15 mm Hg, and nearly two thirds believed the cut-off for ACS was higher than the currently suggested consensus definition (20 mm Hg). In 67.8% of respondents, organ dysfunction was only considered a problem with IAP of 20 mm Hg or higher. IAP was measured most frequently via the bladder (91.9%), but the majority reported that they instilled volumes well above the current guidelines. Surgical decompression was frequently used to treat IAH/ACS, whereas medical management was only attempted by about half of the respondents. Decisions to decompress the abdomen were predominantly based on the severity of IAP elevation and presence of organ dysfunction (74.4%). Overall knowledge scores were low (43 +/- 15%); respondents who were aware of the WSACS had a better score compared to those who were not (49.6% vs 38.6%, P < 0.001). Conclusions: This survey showed that although most responding clinicians claim to be familiar with IAH and ACS, knowledge of published consensus definitions, measurement techniques, and clinical management is inadequate

Intra-abdominal hypertension in patients with severe acute pancreatitis

INTRODUCTION: Abdominal compartment syndrome has been described in patients with severe acute pancreatitis, but its clinical impact remains unclear. We therefore studied patient factors associated with the development of intra-abdominal hypertension (IAH), the incidence of organ failure associated with IAH, and the effect on outcome in patients with severe acute pancreatitis (SAP). METHODS: We studied all patients admitted to the intensive care unit (ICU) because of SAP in a 4 year period. The incidence of IAH (defined as intra-abdominal pressure ≥ 15 mmHg) was recorded. The occurrence of organ dysfunction during ICU stay was recorded, as was the length of stay in the ICU and outcome. RESULTS: The analysis included 44 patients, and IAP measurements were obtained from 27 patients. IAH was found in 21 patients (78%). The maximum IAP in these patients averaged 27 mmHg. APACHE II and Ranson scores on admission were higher in patients who developed IAH. The incidence of organ dysfunction was high in patients with IAH: respiratory failure 95%, cardiovascular failure 91%, and renal failure 86%. Mortality in the patients with IAH was not significantly higher compared to patients without IAH (38% versus 16%, p = 0.63), but patients with IAH stayed significantly longer in the ICU and in the hospital. Four patients underwent abdominal decompression because of abdominal compartment syndrome, three of whom died in the early postoperative course. CONCLUSION: IAH is a frequent finding in patients admitted to the ICU because of SAP, and is associated with a high occurrence rate of organ dysfunction. Mortality is high in patients with IAH, and because the direct causal relationship between IAH and organ dysfunction is not proven in patients with SAP, surgical decompression should not routinely be performed

Intra-abdominal hypertension and abdominal compartment syndrome in pancreatitis, paediatrics, and trauma

Intra-abdominal hypertension (IAH) is an important contributor to early organ dysfunction in trauma and sepsis. However, relatively little is known about the impact of intra-abdominal pressure (IAP) in general internal medicine, pregnant patients, and those with obesity or burns. The aim of this paper is to review the pathophysiologic implications and treatment options for IAH in these specific situations. A MEDLINE and PubMed search was performed and the resulting body-of-evidence included in the current review on the basis of relevance and scientific merit. There is increasing awareness of the role of IAH in different clinical situations. Specifically, IAH will develop in most (if not all) severely burned patients, and may contribute to early mortality. One should avoid over-resuscitation of these patients with large volumes of fluids, especially crystalloids. Acute elevations in IAP have similar effects in obese patients compared to non-obese patients, but the threshold IAP associated with organ dysfunction may be higher. Chronic elevations in IAP may, in part, be responsible for the pathogenesis of obesity-related co-morbid conditions such as hypertension, pseudotumor cerebri, pulmonary dysfunction, gastroesophageal reflux disease, and abdominal wall hernias. At the bedside, measuring IAP and considering IAH in all critical maternal conditions is essential, especially in preeclampsia/eclampsia where some have hypothesized that IAH may have an additional role. IAH in pregnancy must take into account the precautions for aorto-caval compression and has been associated with ovarian hyperstimulation syndrome. Recently, IAP has been associated with the cardiorenal dilemma and hepatorenal syndrome, and this has led to the recognition of the polycompartment syndrome. In conclusion, IAH and ACS have been associated with several patient populations beyond the classical ICU, surgical, and trauma patients. In all at risk conditions the focus should be on the early recognition of IAH and prevention of ACS. Patients at risk for IAH should be identified early through measurements of IAP. Appropriate actions should be taken when IAP increases above 15 mm Hg, especially if pressures reach above 20 mm Hg with new onset organ failure. Although non-operative measures come first, surgical decompression must not be delayed if these fail. Percutaneous drainage of ascites is a simple and potentially effective tool to reduce IAP if organ dysfunction develops, especially in burn patients. Escharotomy may also dramatically reduce IAP in the case of abdominal burns

Moxifloxacin dosing in post-bariatric surgery patients

Introduction Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin concentrations are achieved in this population. Methods In this modelling and simulation study we used data from a trial on moxifloxacin PK. In this trial, volunteers who had previously undergone bariatric surgery (at least 6 months prior to inclusion), received two doses (intravenous and oral) of 400mg moxifloxacin administered on two occasions. Results In contrast to other papers, we found that moxifloxacin PK were best described by a three compartmental model using lean body mass (LBM) as a predictor for moxifloxacin clearance. Furthermore, we showed that the probability of target attainment for bacterial eradication against a hypothetical Streptococcus pneumoniae infection is compromised in patients with higher LBM, especially when targeting microorganisms with minimum inhibitory concentrations (MICs) of 0.5mgl-1 or higher (probability of target attainment (PTA) approaching zero). When considering the targets for suppression of bacterial resistance formation, even at MIC values as low as 0.25mgl-1, standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78kg or higher, the probability of hitting this target approaches zero. Conclusions Throughout our PK-PD simulation study, it became apparent that, whenever optimal bacterial resistance suppression is deemed necessary, the standard moxifloxacin dosing will not be sufficient. Furthermore, our study emphasizes the need for a LBM based individualized dosing of moxifloxacin in this patient population