Multiple Organ Failure Syndrome Research Articles

Intraabdominal Hypertension and Abdominal Compartment Syndrome in Trauma: Pathophysiology and Interventions

Intraabdominal hypertension and abdominal compartment syndrome are increasingly recognized as potential complications in patients who have significant intraabdominal trauma. Intraabdominal hypertension and abdominal compartment syndrome affect all body systems, most notably the cardiac, respiratory, renal, and neurologic systems. This complication also affects blood flow to various intraabdominal organs and may play a significant role in the sepsis and multiple organ failure syndrome seen in many trauma patients. Nursing knowledge of the risk factors and clinical signs of intraabdominal hypertension and abdominal compartment syndrome can reduce the morbidity and mortality associated with this syndrome.

A severity score for spontaneous canine acute pancreatitis.

To derive a severity score for spontaneous canine acute pancreatitis applicable to general practice. Cohort study of canine pancreatitis cases. Cases (n = 68) of spontaneous canine acute pancreatitis presented to general practitioners were identified among accessions to Veterinary Pathology Services Brisbane. The primary veterinarian was surveyed by telephone to ascertain the outcome of each case. Scores were assigned for extent of hyperamylasaemia, hyperlipasaemia and number of organ systems other than the pancreas compromised. The probability of mortality with each score of each analyte was calculated. The strength of interaction between scores for each analyte and mortality rate was assessed by chi-square analysis where appropriate. Relationships between the organ system score, other physiological variables and likelihood of euthanasia were analysed. Scores derived mathematically from analysis of enzyme activities had poor abilities to predict mortality. The score based upon the number of organ systems compromised showed good ability to predict mortality and the interaction between the organ system score and mortality rate was significant by chi-square analysis (P < 0.01). Distribution of data within the amylase and lipase scores was not compatible with chi-square analysis. Assessment of severity of spontaneous canine acute pancreatitis using pancreatic enzyme activities is potentially inaccurate. The use of a severity score based upon organ system compromise was more accurate in determining the likelihood of mortality in spontaneous canine acute pancreatitis. This is compatible with the hypothesis that severe canine acute pancreatitis is a multiple organ failure syndrome.

Histochemical and ultrastructural study of skeletal muscle in patients with sepsis and multiple organ failure syndrome (MOFS).

Muscle biopsies for histochemical and ultrastructural analysis were obtained from seven critically ill patients admitted to the Intensive Care Unit of the "Domingo Luciani" Hospital, Caracas, Venezuela. The sample included two patients with sepsis of abdominal origin, and five that presented sepsis/MOFS, with renal, hepatic, and respiratory disturbances and muscular weakness. Sections were examined for myosin adenosine triphosphatase (ATPase) after pre-incubation with both acid buffer (pH 4.37 and 4.6) and alkaline buffer (pH 10.3), for reduced nicotinamide dinucleotide diaphorase (NADHd), and for alpha-glycerophosphate dehydrogenase (alpha-GPDH). Sections were stained with hematoxilin and eosin to look for pathological changes and examined with a transmission electron microscope. Skeletal muscle of patients in early stage of sepsis showed a normal aspect with light microscopy, but at the ultrastructural level some of the fibres showed atrophy and some capillaries looked altered. Patients with sepsis/MOFS exhibited an evident muscle disorder with oedema, infiltrate, atrophy and segmental necrosis. All fibre types showed decrease in diameter; specially fibre types IIA and IIB. Intramuscular capillaries were thickened and occluded, indexes of capillarity were slightly reduced, and fibre oxidative activity was decreased. At ultrastructural level fibres showed severe atrophy, contractile system disorganization and segmental necrosis. Capillaries were also altered and the mononuclear cell infiltrate was abundant and represented by macrophages, lymphocytes and mastocytes.

Retroperitoneal edema: sonographic mimic of retroperitoneal fluid collection.

The sonographic finding of an anechoic retroperitoneal abnormality suggests a fluid collection (e.g., abscess, urinoma, hematoma). Our study was performed to evaluate cases in which this sonographic finding appeared to be a manifestation of systemic edema. Inpatient sonograms performed over a 40-month period were reviewed for the presence of anechoic areas suggestive of fluid collection in the retroperitoneum of the flank. Records of patients with such findings were reviewed for evidence of retroperitoneal abscess, urinoma, or hemorrhage, as well as for the presence and cause(s) of peripheral edema. Of the 29 patients identified with sonographic findings suspicious for retroperitoneal fluid collection, 13 (45%) had no cause for and no clinical evidence of focal retroperitoneal collection. All 13 patients had peripheral edema attributable to hypoalbuminemia, congestive heart failure, overhydration, cirrhosis, and/or the systemic inflammatory response (multiple organ failure) syndrome. Resolution of the retroperitoneal abnormality following therapy for congestive heart failure was documented in one case, and CT scan confirmed retroperitoneal edema in another. Anechoic regions that represent edema can be seen on sonograms of the retroperitoneum in patients with conditions that cause edema in other regions. The possibility of edema mimicking a fluid collection should be particularly considered prior to invasive procedures in the retroperitoneum.

Bioactivation of leukotoxins to their toxic diols by epoxide hydrolase

Leukotoxin is a linoleic acic oxide produced by leukocytes and has been associated with the multiple organ failure and adult respiratory distress syndrome seen in some severe burn patients. Leukotoxin has been reported to be toxic when injected into animals intravenously. Herein, we report that this lipid is not directly cytotoxic in at least two in vitro systems. Using a baculovirus expression system we demonstrate that leukotoxin is only cytotoxic in the presence of epoxide hydrolases. In addition, it is the diol metabolite that proves toxic to pulmonary alveolar epithelial cells, suggesting a critical role for the diol in leukotoxin-associated respiratory disease. In vivo data also support the toxicity of leukotoxin diol. For the first time we demonstrate that soluble epoxide hydrolase can bioactivate epoxides to diols that are apparently cytotoxic. Thus leukotoxin should be regarded as a protoxin corresponding to the more toxic diol. This clearly has implications for designing new clinical interventions.

Skeletal-muscle ultrastructural pathology in patients with sepsis and multiple organ failure syndrome (MOFS)

To date the most accepted definition of sepsis includes the suspicion of infection plus the systemic response to it (tachypnea, tachycardia and hypothermia or hyperthermia). This condition could lead to the so called multiple organ failure syndrome (MOFS) when there are evidences of flinctional compromise in two or more systems. Muscle weakness and wasting are common findings in those patients. The skeletal muscle histopathology in patients with those two conditions has been poorly studied. The only electron microscopic investigation we could find describes alterations in muscle fibers and endplates.In this work we describe the whole spectrum of changes found in skeletal muscle of patients suffering from sepsis and MOFS.Five patients recluded in an Intensive Care Unit were selected, two had a diagnosis of sepsis, and three presented MOFS. Needle muscle biopsies from quadriceps femoris muscle were obtained. Tissue samples were processed with routine techniques for transmission electron microscopy and observed in a Hitachi H-500 electron microscope.

Detection of Intestinal Bacterial Translocation Using PCR

Microbial translocation has been suspected to be a major contributing factor in the development of sepsis of unknown origin and multiple organ failure syndrome, but there are currently no tests capable of detecting and quantitating translocation sequentially in humans. The purpose of this study was to develop a sensitive polymerase chain reaction (PCR) test to detectEscherichia coli(E. coli) DNA in the blood of animals after inducing bacterial translocation from the gut. DNA was extracted from blood and primers were used to amplify an 800-bp gene fragment ofE. coliby 30-cycle PCR. Detection by southern blotting achieved a sensitivity of 10–100 organisms per 0.3 cc blood. Experimental groups included mice gavaged with 1010E. colifollowed by 20% body surface area thermal injury, or no injury. Controls included burn only and no treatment groups. Blood was obtained by cardiac puncture 1 hr after burn. Cultures were done on blood samples from all groups. More animals in the burn/gavage group had positive bacterial cultures. All controls were culture negative.E. colidetection by PCR was 100% sensitive in culture positive animals with detection in the gavage/burn group higher than that in all other groups. PCR was negative for all mice without treatment. Several culture negative animals had detectable bacterial DNA by PCR. This highly sensitive and specific method can be used repeatedly to test the blood of patients for the presence of microbial DNA, which could be originating from the gut.

Hepatic hypoperfusion after intestinal reperfusion

Intestinal ischemia-reperfusion injury (IIR) induces hepatic and pulmonary dysfunction and thus has been used as a model of multiple organ failure syndrome. This study examines the hypothesis that hepatic blood flow is markedly reduced in this injury model. Sprague-Dawley rats underwent 120 minutes of intestinal ischemia and 60 minutes of reperfusion (IIR). Hepatic blood flow was measured with radiolabeled microspheres and Doppler flow probes. Hepatic dysfunction was quantitated by measuring bile flow and serum alanine aminotransferase and hepatic tissue adenosine triphosphate levels. Sham-operated animals served as controls. Intestinal ischemia reduced portal flow by 66% when compared with sham-operated animals (p = 0.0001) but had no effect on hepatic arterial flow. In contrast, reperfusion reduced hepatic artery flow by 80% when compared with controls (p = 0.002) with most of this change occurring within 5 minutes of reperfusion. IIR induced a 63% reduction in bile flow (p < 0.05), a fivefold rise in serum alanine aminotransferase level (p < 0.0002), and a 33% reduction in hepatic adenosine triphosphate level (p < 0.05). These data suggest that IIR induces profound hepatic hypoperfusion, which is temporally related to acute hepatic dysfunction. This observation suggests that hepatic ischemia may contribute to IIR-induced liver injury.

Hepatitis C: indication for anti-viral therapy?

Hepatitis C infection is a frequent indication for liver transplantation. In general, recurrent graft hepatitis is assumed to be mild, but may be the cause of lethal postoperative complications in a small patient population. Out of 500 transplants in 458 patients, 123 patients were transplanted due to hepatitis C infection (26.7%) between September 1988 and April 1994. Cumulative 1- to 6-year patient survival was similar for patients transplanted due to hepatitis C (87.0%) and those transplanted for other indications (86.0%). In patients with hepatitis C virus (HCV), death, in 50% of the cases, was related to HCV recurrence and chronic rejection. Four patients (25.0%) died because of severe infection and multiple organ failure syndrome unrelated to HCV recurrence and chronic rejection. The incidence of retransplantation was similar in HCV (9.8%) and other patients (8.4%). In HCV patients, 6 of 12 retransplantations (50.0%) were performed due to HCV recurrence and chronic rejection. Of 123 HCV patients, 45 experienced histologically proven recurrent graft hepatitis between 2 weeks and 5.5 years after transplantation. The incidence of acute rejection was similar in both groups. The incidence of steroid-resistant rejection was, however, higher in HCV patients (29.3%) than in those transplanted for other indications (14.5%; P < or = 0.05). Furthermore, there was a significant association between acute rejection and the development of recurrent graft hepatitis. In conclusion, patients with hepatitis C may be transplanted with as good patient and graft survival rates as patients transplanted for other indications. However, the combination of recurrent graft hepatitis and chronic rejection remains the most limiting factor for some of these patients, which strengthens the necessity for a specific anti-viral therapy.

Antioxidants attenuate endotoxin-induced activation of alveolar macrophages

Endotoxin (lipopolysaccharide [LPS]) stimulation of tissue-fixed macrophages induces the generation of toxic oxidants. However, recent studies also implicate redox changes in both the signal transduction pathways for cytokine genes and the generation of physiologically active arachidonic acid metabolites. Because cytokines and arachidonic acid metabolites initiate and perpetuate deleterious systemic inflammatory responses, we tested whether macrophage activation could be modulated by antioxidants. Rabbit alveolar macrophages were obtained by bronchoalveolar lavage, isolated, treated with the antioxidants vitamin E or N-acetylcysteine (NAC), and stimulated with an optimal dose of LPS (10 ng/ml). Assays were performed for tumor necrosis factor (TNF), procoagulant activity, and prostaglandin E2. Total cellular RNA was extracted for Northern blot analysis of TNF messenger RNA. Exposure of the macrophage to the antioxidants vitamin E and NAC inhibited TNF production, accumulation of TNF messenger RNA, procoagulant activity expression, and prostaglandin E2 production. Macrophage signal transduction of LPS is dependent on the generation of reactive oxygen intermediates that can be blocked both at the level of the lipid membrane (vitamin E) and at the intracellular level (NAC). This suggests a potential therapeutic role for antioxidants is disease states such as adult respiratory distress syndrome and multiple organ failure syndrome, which are characterized by excessive macrophage activation.

Monoethylglycinexylidide as an early predictor of posttraumatic multiple organ failure.

The prognostic value of a dynamic liver-function test, based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX), in predicting multiple organ failure (MOF) was prospectively investigated in 28 critically ill patients after multiple trauma. The MEGX test and conventional static liver tests (bilirubin, aspartate aminotransferase, glutamate dehydrogenase, and factor V) were performed on days 1, 3, 5, and 7 after trauma. Patients were classified by a modified MOF score into a group without (n = 18) and a group with the MOF syndrome (n = 10). One patient who developed MOF on the basis of a bacterial septicemia was excluded from the general evaluation. No significant differences were observed in the MEGX values of the two groups on day 1. All patients who subsequently developed MOF, however, displayed a sharp decrease in their MEGX values between days 1 and 3. Analysis of the data using receiver operating characteristic (ROC) curves revealed that the results of the MEGX test on day 3 provided the greatest discriminating power between patients with and without subsequent MOF. A cut-off MEGX value of 30 micrograms/L on day 3 was associated with a prognostic sensitivity of 89% and a prognostic specificity of 94%.

Multiple organ failure syndrome in the 1990s: Beal AL, Cerra FB. JAMA. 1994;271:226–232

Multiple organ failure syndrome in the 1990s: Beal AL, Cerra FB. JAMA. 1994;271:226–232

Renal support in critically ill patients: Low-dose dopamine or low-dose dobutamine?

Low-dose dopamine has been used in critically ill patients to minimize renal dysfunction without sufficient data to support its use. The aim of this study was to determine whether low-dose dopamine improves renal function, and whether dobutamine, a nondopaminergic inotrope, improves renal function. Prospective, randomized, double-blind trial. Twenty-three patients at risk for renal dysfunction were entered into the study. Five patients were later withdrawn. Study data for the remaining 18 patients were: mean age 55 yrs; mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 18; mean weight 71 kg). The following conditions were present: mechanical ventilation (n = 17 [inverse-ratio ventilation, n = 6]); inotrope administration (n = 11); sepsis (n = 13); and adult respiratory distress syndrome or multiple organ failure syndrome (n = 9). The study patients were administered dopamine (200 micrograms/min), dobutamine (175 micrograms/min), and placebo (5% dextrose) over 5 hrs each in a randomized order. Ventilator settings, fluid management, and preexisting inotropic support were not altered during the study. Systemic hemodynamic values and indices of renal function (4-hr urine volume, fractional excretion of sodium, and creatinine clearance) were measured during the last 4 hrs of each infusion. Dopamine produced a diuresis (145 +/- 148 mL/hr) compared with placebo (90 +/- 44 mL/hr; p < .01) without a change in creatinine clearance. Conversely, dobutamine caused a significant increase in creatinine clearance (97 +/- 54 mL/min) compared with placebo (79 +/- 38 mL/min; p < .01), without an increase in urine output. In stable critically ill patients, dopamine acted primarily as a diuretic and did not improve creatinine clearance. Dobutamine improved creatinine clearance without a significant change in urine output.

Predictors of acute respiratory failure after bone marrow transplantation in children.

To determine factors associated with acute respiratory failure after bone marrow transplantation which can be identified before the onset of lung disease. Population-based, retrospective study. A referral-based pediatric intensive care unit and bone marrow transplant center. Thirty-nine patients with lung disease (abnormal chest radiograph or a need for supplemental oxygen) were identified from a group of 318 pediatric bone marrow transplant patients from 1978 to 1988. Thirty-four of 39 patients with complete data were further classified into patients with mild lung disease (recovery without needing endotracheal intubation, n = 16) and patients with acute respiratory failure (requirement for endotracheal intubation, n = 18). Regression analyses were performed to define risk factors for development of respiratory failure (multivariate logistic regression) and for a shortened interval between the identification of lung disease and respiratory failure (Cox proportional hazards analysis). Ninety-three percent (15/16) of patients with mild lung disease survived. Conversely, only 9% (2/23) of patients with respiratory failure survived. Predictors of respiratory failure included graft vs. host disease (odds ratio 28.3, 95% confidence interval 1.9-421, p = .015), a prelung disease (baseline) circulating creatinine concentration of > 1.5 mg/dL (> 132.6 mumol/L) (odds ratio 28.4, 95% confidence interval 1.4-577, p = .029), and male gender (odds ratio 14.6, 95% confidence interval 1-210, p = .049). Predictors of a shortened time to onset of respiratory failure included baseline serum creatinine value of > 1.5 mg/dL (> 132.6 mumol/L) (hazard ratio 6.2, 95% confidence interval 1.5-26.5, p = .013) and baseline total bilirubin concentration > 1.4 mg/dL (> 23.9 mumol/L) (hazard ratio 4.5, 95% confidence interval 0.98-20.7, p = .053). The median time to onset of respiratory failure was 4 days in patients with baseline creatinine values > or = 1.5 mg/dL (> 132.6 mumol/L) and 5 days in patients with baseline bilirubin concentrations > or = 1.4 mg/dL (> 23.9 mumol/L) vs. > 26 days in patients with creatinine < 1.5 mg/dL (< 132.6 mumol/L) and > 29 days in patients with bilirubin < 1.4 mg/dL (< 23.9 mumol/L) (Kaplan-Meier analysis). Renal and liver dysfunction preceded clinical evidence of lung disease in bone marrow transplant patients who developed respiratory failure. Lung disease leading to respiratory failure and adult respiratory distress syndrome appears to develop as one component of the multiple organ failure syndrome in pediatric bone marrow transplant patients.

NEPHROTOXICITY FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION

Nephrotoxicity represents a serious side effect of immunosuppression following liver transplantation. In order to compare the nephrotoxic action of CsA and FK506 in a clinical setting, we evaluated the incidence of early and late nephrotoxicity in 121 patients, 60 of whom were randomly assigned to CsA- and 61 to FK506-based immunosuppression. Early postoperative renal insufficiency (between PODs 0 and 30; SCr 1.5-3 mg/dl) was observed to a similar extent in patients treated with CsA (38.3%) and FK506 (42.6%). Early postoperative acute renal failure (ARF) (SCr > 3 mg/dl) was observed in 18.0% of patients in the FK506 treatment group and 18.3% of patients receiving CsA therapy. Approximately half the patients with ARF required hemodialysis (CsA: 11.7%; and FK506: 8.2%). All patients with early postoperative ARF requiring hemodialysis survived for more than one year. New onset of late ARF (between PODs 30 and 365) was observed in 6.6% of patients receiving FK506 therapy and in 1.7% in the CsA treatment group as a result of severe infection with multiple organ failure syndrome (MOFS). There was 100% mortality in patients with late ARF requiring hemodialysis. Etiology and prognosis of early and late ARF seem to be completely different. Early ARF was associated with severe coagulopathy and a rise in bilirubin and free hemoglobin, and was accompanied by impaired liver function. Mean onset of hemodialysis in CsA-treated patients was POD 1 and in FK506-treated patients POD 6, which disclosed a different time course of drug-specific nephrotoxicity of CsA and FK506 in early ARF. In contrast, late ARF occurred in both treatment groups only as a part of the MOFS in association with severe infections, an observation consistent with the assumption of overimmunosuppression rather than a primary nephrotoxic effect. Late renal insufficiency appeared in 23.3% of CsA- and in 29.4% of FK506-treated patients, and represented a slowly progressing form of drug-specific nephrotoxicity of CsA and FK506. These preliminary results demonstrate a similar outcome in terms of both early and late nephrotoxicity, but longer follow-up will delineate the overall efficacy and toxicity in humans.

Agonist-Induced Peroxynitrite Production from Endothelial Cells

Nitric oxide reacts with superoxide to form peroxynitrite, a potential mediator of oxidant-induced cellular injury. The endothelium is a primary target of injury in many pathological states, including acute lung injury, sepsis, multiple organ failure syndrome, and atherosclerosis, where enhanced production of nitric oxide and superoxide occurs simultaneously. It was hypothesized that stimulation of endothelial cell nitric oxide production would result in formation of peroxynitrite. Immediate oxidant production was detected by luminol- and lucigenin-enhanced chemiluminescence from cultured bovine aortic endothelial cells exposed to bradykinin or to the calcium ionophore A23187. Luminol-enhanced chemiluminescence was efficiently inhibited by the nitric oxide synthase inhibitor nitro-L-arginine methyl ester and by superoxide dismutase, implying dependence on the presence of both nitric oxide and superoxide for oxidant production. Inhibition of luminol-enhanced chemiluminescence by nitro-L-arginine methyl ester was partially reversed by L-arginine, but not by D-arginine. Cysteine, methionine, and urate, known inhibitors of peroxynitrite-mediated oxidation, inhibited luminol-enhanced chemiluminescence, while the hydroxyl radical scavengers, mannitol and dimethylsulfoxide, and catalase did not. Bicarbonate increased luminol-enhanced chemiluminescence in a concentration-dependent manner. Superoxide production, detected by lucigenin-enhanced chemiluminescence, was slightly increased in the presence of nitro-l-arginine methyl ester, suggesting that endothelial cell-produced superoxide was partially metabolized by reaction with nitric oxide. These results are consistent with agonist-induced peroxynitrite production by endothelial cells and suggests that peroxynitrite may have an important role in oxidant-induced endothelial injury.

Relaparotomies after ruptured abdominal aortic aneurysm repair

The outcome of ruptured abdominal aortic aneurysm repair was reviewed in 83 consecutive patients with special emphasis on the influence of subsequent laparotomy. The overall 30-day mortality was 47%. Causes of death were exsanguination in six, cardiac failure in 15, uncontrolled hypotension in six, multiple organ failure (MOF) in nine, adult respiratory distress syndrome in one and sepsis in two patients. Thirty-three relaparotomies were performed in 21 patients after a mean interval of 10 days. Suspected intraabdominal haemorrhage was the indication in 15 and sepsis in 18 cases. The preoperative diagnosis proved to be correct in 12/15 (80%) and 11/18 (61%) instances, respectively. Negative explorations were mainly performed in patients with an established MOF syndrome. Relaparotomies were associated with a significantly (p < 0.05) increased mortality of 76%. The complications that give rise to the need for surgical reintervention are usually accompanied by a clinical deterioration of the patient and inevitably reduce the chances of survival. However, until a reliable predictor of mortality is developed, treatment should not be denied in individual cases.

Multiple organ failure syndrome

Although many new areas of research are directed at the regulatory aspects of the metabolic response, the prognosis of MOF remains poor. Critical care nurses, challenged to provide a supportive environment during this life-threatening syndrome, must understand its onset, clinical patterns, and prolonged support required by patients. Such knowledge will enable critical care nurses to detect subtle changes while monitoring clinical status, and facilitate timely interventions in order to decrease the morbidity and mortality associated with MOF.

DIVING INJURIES

During a 5-year period from January 1987 through January 1992, 58 patients were admitted to the Allegheny General Hospital trauma center for non-scuba, non-suicidal diving injuries. There were 46 men and 12 women (mean age, 23 years). Forty-five patients were injured in swimming pools. Twenty-two patients had blood alcohol levels > 100 mg/dL. Cervical spine injury was the most common pathologic entity encountered in this group of patients. Closed head injury, pelvic fracture, thoracic vertebral fracture, and rib fractures were other injuries identified. Some patients had multiple organ failure syndrome. Aquatic recreational activities carry a risk for injury that is preventable. The mechanism, clinical data, and complications of 58 patients are presented and the importance of prevention is discussed.

Plasma lipid peroxidation in critically ill patients: Importance of mechanical ventilation

Oxygen free radicals may be implicated in the pathogenesis of both ischemia-reperfusion damage and in circulatory shock. The attack on the cell membrane by free radicals leads to lipid peroxidation, which can be assessed by the plasma malondialdehyde (MDA) level. The aim of this study was to determine the importance of lipid peroxidation in critically ill patients. The MDA level was measured by the thiobarbituric acid test. Nineteen patients at an early stage of circulatory shock, 11 patients in the weaning period of ventilation, 9 gastro-enterological patients without cardio-circulatory distress or sepsis, and 9 healthy volunteers were studied. The MDA level was higher in critically ill patients than in control subjects (61% in patients with shock and 40% in patients on mechanical ventilation). No correlation was found between the MDA level and the outcome: multiple organ failure or acute respiratory distress syndrome. This proposal leads to the question of systematic antioxidant therapy in intensive care patients.