Necrotizing Soft-Tissue Infections

*Department of Surgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina †Department of Surgery, University Hospital Zurich, Zurich, Switzerland. Reprints: Pierre-Alain Clavien, MD, PhD, Department of Surgery, University Hospital Zurich, Ramistrasse 100, CH-8091, Zurich, Switzerland. E-mail: [email protected]. Disclosure: The authors declare that they have nothing to disclose.

Introduction: Hypertriglyceridemia is an established risk factor for acute pancreatitis. This study seeks to evaluate the effect of serum triglycerides on the development of persistent or multiple organ failure in patients with acute pancreatitis. Methods: A retrospective cohort study was conducted using data from an integrated healthcare system. Patients hospitalized for acute pancreatitis between January 1, 2006 and December 31, 2013 were included in the study. Triglyceride levels measured prior to and within 72 hours of admission were compared. In addition, the impact of serum triglycerides on the development of persistent or multiple organ failure during hospitalization for acute pancreatitis was assessed using Poisson regression models adjusting for age and sex. Results: Among 2,519 patients, 267 patients (10.6%) developed organ failure, of which 75 patients (28.1%) developed multiple system organ failure and 82 patients (30.7%) developed persistent organ failure. Serum triglyceride levels in patients who developed organ failure were initially much higher than in patients who did not develop organ failure, but by 72 hours into the admission, approached levels of the patients who did not develop organ failure. Approximately 7% of patients had very high serum triglyceride levels (>500 mg/dL), which correlated with similarly high triglycerides levels prior to admission. Conclusion: Increased TG levels were associated with the development of multiple or persistent organ failure in this study of patients hospitalized with acute pancreatitis. Patients with high triglyceride levels at the time of admission for acute pancreatitis were likely to have high triglyceride levels prior to admission.

Spinal cord injury (SCI) is a devastating event that results in significant physical disabilities for affected individuals. Apart from local injury within the spinal cord, SCI patients develop a variety of complications characterized by multiple organ dysfunction or failure. These disorders, such as neurogenic pain, depression, lung injury, cardiovascular disease, liver damage, kidney dysfunction, urinary tract infection, and increased susceptibility to pathogen infection, are common in injured patients, hinder functional recovery, and can even be life threatening. Multiple lines of evidence point to pathological connections emanating from the injured spinal cord, post-injury systemic inflammation, and immune suppression as important multifactorial mechanisms underlying post-SCI complications. SCI triggers systemic inflammatory responses marked by increased circulation of immune cells and pro-inflammatory mediators, which result in the infiltration of inflammatory cells into secondary organs and persistence of an inflammatory microenvironment that contributes to organ dysfunction. SCI also induces immune deficiency through immune organ dysfunction, resulting in impaired responsiveness to pathogen infection. In this review, we summarize current evidence demonstrating the relevance of inflammatory conditions and immune suppression in several complications frequently seen following SCI. In addition, we highlight the potential pathways by which inflammatory and immune cues contribute to multiple organ failure and dysfunction and discuss current anti-inflammatory approaches used to alleviate post-SCI complications. A comprehensive review of this literature may provide new insights into therapeutic strategies against complications after SCI by targeting systemic inflammation.

M ajor liver resections and partial orthotopic liver transplantation (OLT) have become established procedures in liver surgery; for many patients, these techniques offer the only curative option. Yet, many patients develop postoperative complications because the remnant livers or grafts are too small or of poor quality to sustain sufficient organ function. This somewhat new and poorly defined phenomenon has been termed ‘‘small-for-size syndrome’’ (SFSS) to describe this scenario. The concept is, in fact, not a new one, because as early as the 1970s, Thomas E. Starzl described the complicated postoperative course of a young woman subjected to an almost 90% hepatectomy and who was subsequently characterized by prolonged hyperbilirubinemia, encephalopathy, and coagulopathy. In an unconventional way for a review, we will start with three case reports to illustrate the scope and clinical relevance of SFSS after liver surgery and transplantation. Case 1: A 47-year-old healthy man, whose wife was listed for OLT due to a symptomatic nonresectable hemangioendothelioma of the liver, offered to be considered for living donor liver transplantation (LDLT). Following the standard work-up for this procedure, he underwent a right hemi-hepatectomy including the middle hepatic vein to serve as allograft for his wife. The remnant left hemi-liver was estimated by computed tomographic (CT) volumetry to weigh 450 g, i.e., around 32% of the whole liver. The ratio of the remnant liver weight to body weight (RLBW) was 0.65%. The donor had a difficult postoperative course developing mild encephalopathy and hyperbilirubinemia lasting 20 days peaking at 178 lmol/L (10.4 mg/ dL) by day five, and severe coagulopathy (prothrombin time <30%) that normalized by day 7. The donor eventually recovered fully, and was discharged in good general condition 22 days after surgery. Case 2: A 42-year-old male was listed for OLT because of Child B cirrhosis (Model for End-Stage Liver Disease [MELD] score: 21) and a small (3 cm) hepatocellular carcinoma (HCC) related to hepatitis B virus infection. He received the right hemi-liver containing the middle hepatic vein from his wife (graft weighing 620 g), who had an uneventful postoperative course. The ratio of graft size in grams to her husband’s body weight (80 kg) (graft-to-recipient weight ratio [GRWR]) was 0.7%. The postoperative period was complicated by encephalopathy, hyperbilirubinemia (up to 262 lmol/L, 15.3 mg/dL) for 2 weeks, and prolonged coagulopathy with a factor V level below 20% at day 4. As a result of the delayed graft function, the patient required intensive care unit treatment for 1 week before the liver graft function improved. He was able to be discharged in good general condition on postoperative day 21. Case 3: A 58-year-old male presented with multiple colorectal liver metastases in the right hemi-liver as well as in segment II, III, and 10 months after resection of the primary rectal tumor followed by 5 cycles of chemotherapy containing Folfox and Avastin. A Abbreviations: CALI, chemotherapy-associated liver injury; CT, computed tomography; DOI, 2,5-dimethoxy-4-iodoamphetamine; EHPBA, European Hepato-Pancreatico-Biliary Association; GRWR, graft-to-recipient weight ratio; HCC, hepatocellular carcinoma; IHPBA, International Hepato-PancreaticoBiliary Association; IL-6, interleukin-6; LDLT, living donor liver transplantation; MELD, Model for End-Stage Liver Disease; OLT, orthotopic liver transplantation; PTX, pentoxifylline; RLBW, remnant liver to body weight; SFSS, small-for-size syndrome; TNF, tumor necrosis factor. From the Swiss Hepato-Pancreatico-Biliary and Transplantation Center, Department of Surgery, University of Zurich, Zurich, Switzerland Funded in part by Grants from the Swiss National Foundation to P.A.C. (SNF 3200B0-109906), Krebsliga Zurich, Switzerland and Sassella Stiftung Zurich, Switzerland, also to P.A.C. Presented as a Thomas E. Starzl Transplant Surgery State-of-the-Art Lecture at the 60th Annual Meeting of the American Association for the Study of Liver Diseases; October 30-November 3, 2009; Boston, MA. This article is dedicated to Thomas E. Starzl for his lifelong contribution to liver surgery and transplantation. Address reprint requests to: Pierre-Alain Clavien, M.D., Ph.D., Department of Surgery, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland. E-mail: clavien@access.uzh.ch; fax: þ41 44 255 44 49. CopyrightVC 2010 by the American Association for the Study of Liver Diseases. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hep.23713 Potential conflict of interest: Nothing to report.

Journal-related Activities and Other Special Activities at the 2011 American Society of Anesthesiologists Annual Meeting

To determine clinician accuracy in the identification and prediction of multiple organ dysfunction syndrome. Prospective cohort study. University of Michigan's C.S. Mott Children's Hospital PICU. Patients admitted to the PICU with an anticipated PICU length of stay greater than 48 hours. None. For each patient, the clinical team (attending, fellow, resident/nurse practitioner) was surveyed regarding existing and anticipated organ dysfunction. The primary outcomes were clinicians' accuracy at identifying multiple organ dysfunction syndrome and predicting new or progressive multiple organ dysfunction syndrome, compared to the objective assessment of multiple organ dysfunction syndrome using Proulx criteria. We also measured sensitivity, specificity, negative and positive predictive values, and negative and positive likelihood ratios of clinician assessments. We tested for differences in accuracy by clinician type using chi-square tests. Clinicians rated their confidence in prediction on a 5-point Likert scale. There were 476 eligible PICU admissions, for whom 1,218 surveys were completed. Multiple organ dysfunction syndrome was present in 89 patients (18.7%) at enrollment, and new or progressive multiple organ dysfunction syndrome occurred in 39 (8.2%). Clinicians correctly identified multiple organ dysfunction syndrome with 79.9% accuracy and predicted additional organ dysfunction with 82.6% accuracy. However, the positive and negative likelihood ratios for new or progressive multiple organ dysfunction syndrome prediction were 3.0 and 0.7, respectively, indicating a weak relationship between the clinician prediction and development of new or progressive multiple organ dysfunction syndrome. The positive predictive value of new or progressive multiple organ dysfunction syndrome prediction was just 22.1%. We found no differences in accuracy by clinician type for either identification of multiple organ dysfunction syndrome (80.2% vs 78.2% vs 81.0%; p = 0.57) or prediction of new or progressive multiple organ dysfunction syndrome (84.8% vs 82.8% vs 80.3%; p = 0.26) for attendings, fellows, and residents/nurse practitioners, respectively. There was a weak correlation between the confidence and accuracy of prediction (pairwise correlation coefficient, 0.26; p < 0.001). PICU clinicians correctly identified multiple organ dysfunction syndrome and predicted new or progressive multiple organ dysfunction syndrome with 80% accuracy. However, only 8% of patients developed new or progressive multiple organ dysfunction syndrome, so accuracy was largely due to true negative predictions. The positive predictive value for new or progressive multiple organ dysfunction syndrome prediction was just 22%. Accuracy did not differ by clinician type, but was correlated with self-rated confidence and was higher for negative predictions.

BackgroundThe aim of this study was to assess the incidence of organ failure in trauma patients treated in an intensive care unit (ICU), and to study the relationship between organ failure and long-term survival and functional status.MethodsThis is a cohort study of all adult ICU trauma patients admitted to a university hospital during 1998 to 2003. Organ failure was quantified by the Sequential Organ Failure Assessment (SOFA) score. A telephone interview was conducted in 2005 (2 to 7 years after trauma) using the Karnofsky Index to measure functional status, and the Glasgow Outcome Score to measure recovery.ResultsOf the 322 patients included, 47% had multiple organ failure (MOF), and 28% had single organ failure. In a Cox regression, MOF increased the overall risk of death 6.0 times. At follow-up, 242 patients (75%) were still alive. Patients with MOF had 3.9 times greater odds for requiring personal assistance in activities of daily living compared to patients without organ failure. Long-term survival and functional status were the same for patients suffering single organ failure and no organ failure. Complete recovery occurred in 52% of survivors, and 87% were able to look after themselves.ConclusionAlmost half of the ICU trauma patients had MOF. While single organ failure had no impact on long-term outcomes, the presence of MOF greatly increased mortality and the risk of impaired functional status. MOF expressed by SOFA score may be used to define trauma patients at particular risk for poor long-term outcomes.

Sepsis is one of the main problems in medicine due to its complexity from pathophysiology, clinical, and therapeutic standpoints. Although several definitions have been proposed for this syndrome, it can in general be assumed that it represents the clinical manifestation of a system response of the body to infection or to an inflammatory-associated acute disease [1,2]. Despite advances in medical practice, sepsis, severe sepsis, and septic shock, associated with different grading of organ(s) dysfunction/failure, are conditions that significantly limit quality of life and the ultimate survival of intensive care unit (ICU)patients. In any case, the health cost implications remain exorbitant [3]. Mortality rates as a result of sepsis are associated with a pattern characterized by progressive dysfunction/failure of non-pulmonary organ systems and, in particular, worsening neurologic, coagulation, and renal dysfunction over the first three days. Although initial pulmonary dysfunction is common in patients with sepsis syndrome, it is not associated with an increased mortality rate [4]. In five recent clinical trials that enrolled a total of 5661 patients with severe sepsis — the criteria being evidence of infection, systemic inflammatory response syndrome (SIRS), and at least one organ dysfunction/hypoperfusion — the incidences of septic shock ranged from 52 to 71% in the group of patients with severe sepsis. The mean was 58% [5, 6, 7, 8, 9]. A recent study used the International Classification of Diseases (ICD) nine hospital diagnostic codes for infection and acute organ dysfunction — to estimate 751 000 cases of severe sepsis per annum in the United States [3]. According to this data, septic shock would, therefore, be predicted to occur annually in 435 580 patients in the US. Mortality rate is a consequence of one or more factors such as:age, immunodepression, presence of diseases and/or chronic failure of one or multiple organ system dysfunctions and/or failure [10, 11]. Pathophysiologic mechanisms are basically related to Gram-negative bacteria endotoxin [12], but also Gram-positive micro-organisms, viruses, and mycetes, which are supposedly responsible for the local and systemic release of several mediators that, in turn, might be responsible for the organic response to infection, characterised by cardiovascular instability, hyperthermia, hypothermia, leukocytes, and coagulation alterations as well as by involvement of one or multiple organs [13]. The term sepsis is related to the concept of multiple organ dysfunction syndrome (MODS), which is frequently identified with the end result of infection, although it has been shown that septic syndrome is not specific to infection and can also originate as a result of a variety of non-infectious stimuli such as pancreatitis, burns, and trauma [14]. The American College of Chest Physicians proposed new definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis [15]. Indeed, although remarkable progress has been achieved in defining the pathophysiology of sepsis, the terminology associated with research in this field has remained confusing.

Liver transplantation in patients with multiple organ failures: Feasibility and outcomes

To examine the effect of multiple organ failure after liver transplantation on mortality and resource utilization. Retrospective cohort study. Surgical intensive care unit in a tertiary care university hospital. Consecutive series of 113 adults undergoing liver transplantation between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or had incomplete records (n = 7). None. We prospectively developed definitions for organ failure, and quantitated the frequency and related outcomes for mortality and resource utilization. Multiple organ failure was defined as the presence of two or more organ failures. Patients were grouped according to the presence (n = 31) or absence (n = 65) of multiple organ failure. Preoperative severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE II) and United Network for Organ Sharing (UNOS) scoring systems. Postoperative outcome data, including hospital survival rate, hospital length of stay, and charges were recorded. The frequency of multiple organ failure after liver transplantation was 32%. The mortality rate in the patients who developed multiple organ failure was 42% vs. only 2% in those patients without multiple organ failure (p < .0001). Patients with four or more organ failures had a 100% mortality rate. Postoperative multiple organ failure was associated with increased hospital length of stay (46 +/- 7 days vs. 29 +/- 2 days; p = .026) and increased hospital charges ($271,497 +/- 29,994 vs. $136,372 +/- 8,310; p < .0001). Higher preoperative APACHE II and UNOS scores predicted postoperative multiple organ failure, but were less accurate tools for predicting risk of death. Multiple organ failure is associated with death and increased resource utilization in liver transplantation. Pretransplantation severity of illness, as measured by APACHE II and UNOS scoring systems, is an important determinant of postoperative multiple organ failure and outcome.

Objective To investigate the optimal strategy of fluid resuscitation in the early stage of severe acute pancreatitis (SAP). Methods 60 SAP patients who received treatment in our hospital from March, 2005 to september, 2007 were randomly divided into 4 groups (n = 15) according to the different amounts of crystal and colloid in the daily resuscitation, including crystal group, combined group Ⅰ (the ratio of crystal to colloid was 4 to 1), combined group Ⅱ (the ratio was 3 to 1) and combined group Ⅲ (the ratio was 2 to 1). The levels of hematocrit (HCT), saturation of central vein oxygen (ScvO2), gastric mucosa pH (pHi), serum lactic acid as well as the advent of negative fluid balance, the amount of fluid contained in the third space, mortality rate and the incidence of multiple organ dysfunction syndrome (MODS) in different groups were compared. Results Compared with crystal group, all the parameters were significantly improved in the 3 combined groups (P < 0.05) and the strategy in combined group Ⅲ seemed to be the most effective. HCT in this group of patients was (30.3 ± 7.1) %, ScvO2 was (81.1 ± 16.2) %, pHi was 7.8 ～ 1.5, lactic acid was (1.4 ± 0.6) mmol/L, the advent of negative fluid balance was (77.0 ± 16.8) h, the amount of fluid contained in the third space was(50.2 ± 7.8)ml, mortality rate was 6.7% and MODS incidence was 20%. Conelusions In the early stage of SAP, fluid resuscitation by a combination of crystal and colloid could effectively restore blood volume, reduce the amount of fluid contained in the third space, shorten the duration of positive fluid balance, increase tissue perfusion and oxygen supply, maintain critical organs' function and significantly improve the prognosis of SAP. Key words: Pancreatitis, acute necrotizing; Fluid therapy; Fluid sequestration; Negative balance

To assess the etiologies and outcomes of patients with secondary hemophagocytic lymphohistiocytosis in the PICU. Prospective observational cohort study. A single PICU at a pediatric tertiary hospital in Hanoi, Vietnam. Pediatric patients meeting the criteria for secondary hemophagocytic lymphohistiocytosis. None. Between June 2017 and May 2018, 25 consecutive patients with a mean (SD) age of 23.3 months (21.6 mo) were included. Collected variables included etiologies of hemophagocytic lymphohistiocytosis and clinical and laboratory findings at admission. The Pediatric Index of Mortality 2 score at admission was calculated. Outcomes were death and multiple organ dysfunction. The severity of multiple organ dysfunction was assessed by the Pediatric Logistic Organ Dysfunction 2 score. The mean (SD) Pediatric Index of Mortality 2 predicted mortality rate was 5.6% (7.6%). Cytomegalovirus and Epstein-Barr virus coinfections (60%) were the most common suspected etiology of hemophagocytic lymphohistiocytosis. Other etiologies included Epstein-Barr virus sole infections (20%), cytomegalovirus sole infections (16%), and one unknown cause (4%). Multiple organ dysfunction (excluding hematologic failure) was found in 22 patients (88%) with death occurring in 14 patients (56%). The mean (SD) Pediatric Logistic Organ Dysfunction 2 predicted mortality rate among patients with multiple organ dysfunction was 11.9% (11.2%). Despite having lower Pediatric Index of Mortality 2 predicted mortality rates at admission, Epstein-Barr virus-cytomegalovirus coinfection cases with multiple organ dysfunction had slightly greater Pediatric Logistic Organ Dysfunction 2 predicted mortality rates than Epstein-Barr virus sole infection cases with multiple organ dysfunction: 12.2% (10.5%) versus 11.3% (11.0%). However, these rates were lower than cytomegalovirus sole infection cases with multiple organ dysfunction (14.4% [16.3%]). Area under the curve values for Pediatric Index of Mortality 2 and Pediatric Logistic Organ Dysfunction 2 were 0.74 (95% CI, 0.52-0.95) and 0.78 (95% CI, 0.52-1.00), respectively, suggesting that both scales were fair to good at predicting mortality. Viral infections, particularly Epstein-Barr virus-cytomegalovirus coinfections, were a common cause of secondary hemophagocytic lymphohistiocytosis. The implication of these coinfections on the clinical course of hemophagocytic lymphohistiocytosis needs to be delineated.

The inhibitory effects of YM264, a selective platelet activating factor (PAF) receptor antagonist, and 2-(3-methylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, on mortality, and pancreatic, hepatic, renal and pulmonary dysfunction were evaluated in a rat model of multiple organ failure (MOF) accompanying acute pancreatitis. MOF was produced by intraperitoneal injection of lipopolysaccharide (LPS, 30 mg/kg) in rats with cerulein-induced pancreatitis. LPS dose-dependently increased the mortality in rats with or without pancreatitis. The threshold dose which produced death in rats without pancreatitis was 30 mg/kg. This same dose evoked death in more than 40% of rats with pancreatitis. Time-course changes in serum enzyme and organ myeloperoxidase (MPO) levels were first examined in rats with induced MOF, and the results were compared with those in rats treated with only LPS or cerulein. Pancreatic weight, and serum amylase and lipase levels significantly increased in rats with cerulein-induced pancreatitis despite the presence or absence of LPS, but recovery of these pancreatic dysfunctions was slower in the group given LPS. However, serum GOT, GPT, BUN and creatinine levels were significantly elevated only in MOF rats. In the MOF rats, the MPO level in the lung was significantly elevated and arterial oxygen pressure was decreased, indicating that infiltration of neutrophils into the lung might be involved in pulmonary dysfunction. However, the MPO levels in the pancreas and kidney in the MOF rats were not remarkably different from those in normal rats. The inhibitory effects of YM264 and compound 1 on mortality and organ dysfunction were examined in this MOF model. The 24-h survival rate for rats prophylactically and therapeutically treated with an intravenous infusion of YM264 at 0.1 mg/kg h was significantly higher than that of controls. The 24-h survival rate for rats treated prophylactically by intravenous infusion of 2 mg/kg h of compound 1 was significantly higher than that of control, whereas a beneficial dose of compound 1 was 5 mg/kg h in therapeutically treated rats. Prophylactic treatment with YM264 (0.1 mg/kg h) and compound 1 (2 mg/kg h) ameliorated organ dysfunction in rats with MOF. In conclusion, pancreatic, hepatic, renal and pulmonary dysfunctions are observed in this rat MOF model. The PAF receptor antagonist and neutrophil elastase inhibitor reduce the mortality rate in rats with MOF due to their inhibitory effects on organ dysfunction, indicating that PAF and neutrophil elastase may play important roles in the development of MOF. These results in the present model are largely consistent with those in patients with MOF, indicating that this model is suited for MOF in humans and may be used as a model to test new therapeutic approaches.

Acute febrile illness with Multi Organ Dysfunction Syndrome (MODS) carries significant morbidity and mortality despite standard therapy in intensive care settings. Infections are the most common cause of MODS followed by polytrauma. Present study was undertaken in medical intensive care units of a tertiary hospital to study the aetiology and outcome among patients with acute febrile illness developing MODS. 1) To study the aetiology of acute febrile illness in patients developing MODS. 2) To study the final outcome among these patients. The present study was conducted at a tertiary care hospital in Mysuru, Karnataka, India, over a period of 6 months from July 2013 to December 2013. The Institutional Ethics Committee Approval (IEC) was obtained before the commencement of the study. A total of 213 cases admitted in intensive care unit with acute febrile illness with two or more organ dysfunction were screened for the inclusion and exclusion criterias. A total of 213 cases of acute febrile illness with one or more organ dysfunction were screened. Of the screened patients 75 patients were finally included in the study out of which 46 (61.3%) patients were males and 29 (38.7%) patients were females. Aetiology for acute febrile illness with MODS could be established in 49 (65.3%) patients and it was obscure in 26 (34.7%) patients despite repeated investigations. Dengue infection (29.3%) was the commonest cause of febrile illness with MODS followed by leptospirosis (22.7%). Majority of these patients had haematological derangements (78.7%) and liver function test abnormalities (68%). Out of these 75 cases, 54 (72%) patients recovered completely and 21 (28%) patients died. Among males (N=46), 35 (76.1%) patients recovered and 11 (23.9%) patients died where as among females (N=29), 19 (65.5%) patients recovered and 10 (34.5%) patients died. Mortality was proportionate with the number of organ dysfunction, especially Central Nervous System (CNS) involvement. Incidence of febrile illness with MODS is more prevalent in males but the outcome appears poorer among females. The diagnosis remained obscure in a sizable proportion of these patients. Prognosis was inversely dependent on the number of organs involved especially with CNS manifestations.

Plasma exchange and COVID 19