Impaired antibody production in blunt trauma. Possible role for T cell dysfunction.

This study investigates mechanisms of impaired humoral immune response in a well-defined population of blunt trauma patients (n = 18, Injury Severity Score greater than or equal to 20). Spontaneous and pokeweed mitogen-induced polyclonal immunoglobulin production were assessed in cultures of peripheral blood mononuclear cells. The proliferative response to alloantigen and mitogen was assessed in parallel by the mixed lymphocyte reaction and pokeweed mitogen-induced blastogenesis, respectively. Pokeweed mitogen-induced IgG and IgM production was significantly reduced in trauma patients compared with controls. This effect was not reversed by depletion of adherent cells or by the addition of indomethacin. Exogenous interleukin 2 was also ineffective. However, the addition of normal T cells or supernatants from isoantigen-stimulated cultures of these cells to patient B cell-enriched cultures significantly enhanced (by 1.4- to 5.1-fold) the antibody response to pokeweed mitogen. Thus, suppression of humoral antibody response in blunt trauma patients may be due to failure of T-cell mediated help, resulting in insufficient secretion or activity of cytokines required for adequate B cell activation, proliferation, or differentiation into immunoglobulin-secreting cells.

Bacterial translocation induces procoagulant activity in tissue macrophages. A potential mechanism for end-organ dysfunction.

The ability of bacterial translocation to induce cell-associated procoagulant activity was examined in a rodent model. Intestinal decontamination with streptomycin sulfate and bacitracin followed by oral feeding with a streptomycin-resistant strain of Escherichia coli produced monoassociation of the gastrointestinal tract with this microorganism. Using this model, the rate of bacterial translocation at day 3 increased from 6% (1 of 17) to 90% (28 of 31). Cell-associated procoagulant activity was measured in the mononuclear cell population of mesenteric lymph nodes as well as portal and systemic blood and also in hepatic nonparenchymal cells. In monoassociated animals, the procoagulant activity of mesenteric lymph node mononuclear cells was significantly greater than in control animals at day 3 (210% +/- 28% vs 100% +/- 6%) but not at days 1 or 6. Procoagulant activity of hepatic nonparenchymal cells was elevated in monoassociated animals at days 3 and 6 compared with control animals. Both control and monoassociated animals remained well throughout the experiment. The histologic features of the gastrointestinal tract, mesenteric nodes, and liver did not differ between groups. These studies provide evidence that bacterial translocation, in the absence of external stimuli, is able to induce cell activation at sites remote from the gastrointestinal tract and may therefore contribute to the pathogenesis of multiple organ failure.

Effect of antibiotics and sedatives on normal neutrophil nicotinamide-adenine dinucleotide phosphate-reduced oxidase activity.

The effects of antibiotics and other commonly used medications on the human polymorphonuclear neutrophil leukocytes' (PMNs) nicotinamide-adenine dinucleotide phosphate-reduced (NADPH) oxidase activity have been investigated in vitro. Five antibiotics (penicillin G sodium, cefamandole nafate, metronidazole hydrochloride, clindamycin phosphate, and tobramycin sulfate, and a triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate) and two sedatives (morphine sulfate and diazepam) were incubated with normal human PMNs at therapeutic, infratherapeutic, and supratherapeutic drug levels. The superoxide dismutase-inhibitable, NADPH-dependent reduction of cytochrome C in the PMNs was studied after stimulation with formyl-methionyl-leucine-phenylalanine. Tobramycin sulfate and the triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate significantly reduced the NADPH oxidase activity at all dosages studied. Clindamycin phosphate, morphine sulfate, and diazepam also showed significant reduction at therapeutic and supratherapeutic concentrations. Penicillin G sodium, cefamandole nafate, and metronidazole hydrochloride did not cause a decrease in enzyme activity at any levels tested. We conclude that NADPH oxidase activity can be adversely affected by the circulating levels of common antibiotics and sedatives.

Aggregation by fragilis and non-fragilis Bacteroides strains in vitro.

Bacteroides fragilis is associated with the formation of intra-abdominal abscesses, whereas other Bacteroides species are rarely involved. Since bacterial clumping may contribute to the survival of bacteria in the face of host defence mechanisms, the hypothesis has been put forward that differences in aggregation between fragilis and non-fragilis strains of Bacteroides may account for their differences in survival in vivo. All seven B. fragilis strains tested formed aggregates within 4 h, but strains not associated with intra-abdominal sepsis--B. vulgatus, B. thetaiotaomicron and B. distasonis--did not form aggregates in vitro. Aggregation occurred at 37 degrees C, but not at 4 degrees C or 20 degrees C. Treatment with pronase partially inhibited aggregation. Periodate treatment killed the cells and caused them to form clumps which were distinguishable from the control aggregates. Heat-killed B. fragilis cells formed similar distinct clumps, but cells killed by glutaraldehyde and formaldehyde did so to a lesser degree. No inhibition was found upon addition of carbohydrates, ethylenediaminetetraacetic acid or after treatment with trypsin. These results demonstrate that aggregate formation occurs with B. fragilis strains alone, and that surface proteins probably mediate this interaction.

Reducing the costs of ICU admission in Canada without diagnosis-related or case-mix groupings.

A prospective analysis of the cost of intensive care was carried out on 67 admissions to a multidisciplinary ICU. Admissions were grouped and investigated according to various criteria such as admitting diagnosis, admission status (elective vs emergency), severity of illness and outcome. Total ICU admission costs, total per diem ICU costs and per diem costs divided into fixed and variable cost items for the patient groups are reported. Lower total and per diem ICU charges were observed for elective surgical patients, patients with lower severity of illness as assessed by the Therapeutic Intervention Scoring system and survivors. Emergency admissions were more expensive than elective admissions when compared for total ICU admission costs. Length of stay was a significant factor in overall ICU costs. Within the variable cost items, the diagnostic laboratory was the single most costly item per day. As a result of this analysis, the authors propose several suggestions for reducing ICU costs independent of case-mix or diagnosis-related groupings of ICU patients.

Methyldopa hypersensitivity can mimic acute toxic enterocolitis.

The most widely known hypersensitivity reaction of methyldopa, a drug commonly used in the treatment of hypertension, is seroconversion to a positive result of a direct Coombs' test that may lead to a hemolytic anemia. The authors report a case of an infrequently noted, but serious, hypersensitivity reaction to methyldopa, manifesting primarily as acute toxic enterocolitis. A 63-year-old woman was admitted to hospital and underwent aggressive and prolonged investigation of enterocolitis. Withdrawal of methyldopa gave immediate relief of intestinal problems. Rechallenge precipitated a return of symptoms within 14 hours. It is recommended that periodic blood counts and liver function tests be done on patients treated with methyldopa for hypertension. If any abnormalities are noted the drug should be discontinued.

Mead Johnson Critical Care Symposium for the Practising Surgeon. 1. Transport of critically ill adult patients.

Interhospital transportation of critically ill patients over long distances is common in the tiered health care systems of North America. The authors describe their 1-year experience with a physician-assisted transport system, operating out of the surgical intensive care unit at the Toronto General Hospital. The application of a well-known severity of illness measure (therapeutic intervention scoring system) allowed them to correlate severity of illness, as assessed over the telephone before patient transfer, with eventual outcome after admission to the surgical intensive care unit. Their analysis of 107 critically ill patients transported by this system led them to conclude that the system is reliable and is associated with acceptable morbidity and mortality.

From premise to principle: the impact of the gut hypothesis on the practice of critical care surgery.

Clinical decision making is ideally founded on evidence of efficacy derived from well-designed randomized clinical trials. In reality, such evidence is rarely available to the surgeon caring for the patient with multiple trauma or who is critically ill, and complex management decisions must be made by less rigorous, more subjective means. An understanding of the normal biologic state and its alterations during disease has long been a fundamental component of medical education. Although such an understanding does not provide practitioners with grounds for assuming therapeutic efficacy in a particular patient, it does shape their perception of the important principles that guide the decision-making process. In contrast to evidence-based medicine--the making of therapeutic decisions through the systematic synthesis of results of clinical trials--a knowledge of pathobiology supports a complementary approach that the authors term "inference-based medicine"--the use of insights from studies in basic biology to establish principles that guide the practitioners' approach to groups of patients. The impact of a relatively new area of biologic investigation into the effects of the gut flora on systemic homeostasis, and the perturbations of this process in trauma and critical illness are reviewed. Re-emergence of the "gut hypothesis" has had a relatively modest effect if measured by the introduction of promising new forms of specific therapy. However, these investigations have resulted in a fundamental paradigm shift in two important areas in the practice of trauma and critical care surgery: the use of antimicrobial agents and the route of nutritional support.

Factors predicting discharge from intensive care: a Canadian experience.

This study prospectively analyzed 481 admissions to a multidisciplinary intensive care unit in order to determine factors which may prove helpful in predicting outcome from an intensive care admission. Severity of illness was assessed by the admission acute physiology score and daily therapeutic intervention scoring system. Age, sex, diagnosis upon admission, nature of the admission (medical vs. surgical, emergency vs. elective) were also studied. Our results indicate that the admission acute physiology score during the first three days of the admission and thereafter, the daily therapeutic intervention scores from the previous day are the most reliable predictors of outcome from intensive care. Age was related to outcome only when it was associated with emergency and medical type admissions. A linear logistic regression analysis was used to construct a model predicting mortality within the intensive care unit based on acute physiology score and nature of the admission.

Amphojeloma: antacid impaction in a critically ill patient.

Patients in the intensive care unit seldom have mechanical small-bowel obstruction, and obstruction due to medication bezoars is even less common. A 65-year-old woman, in the intensive care unit because of septic shock and acute renal failure, had a small-bowel obstruction due to Amphojel concretions. Obstruction from such a cause may be prevented by including non-constipating antacids, stool softeners or sorbitol. Aggressive use of H2-antagonists to prevent gastrointestinal bleeding in septic patients will reduce the need for orally administered antacids. When obstruction occurs due to antacid concretions, it may be relieved by passing a long intestinal tube, by giving enemas for colonic obstruction or by operation.

Open or closed diagnostic peritoneal lavage for abdominal trauma? A meta-analysis.

OBJECTIVES: To perform a meta-analysis of prospective, randomized controlled trials comparing the closed and open technique of diagnostic peritoneal lavage (DPL) in trauma patients to determine whether there are any difference in outcomes. METHODS: A search of MEDLINE database of English language articles published from 1977 to 1999 was conducted by using the terms diagnostic peritoneal lavage, trauma, and randomized controlled trials. A manual search and Cochrane Library database search was also conducted. Seven randomized controlled trials, including a total of 1,126 patients were identified that compared closed versus open technique. Two reviewers assessed the trials independently. Trial quality was critically appraised by using the Jadad Instrument, a validated published quality scale. Data extraction of major complications, technical difficulties, procedure times, and false-negative and false-positive rates was carried out. The fixed effects model was used for statistical analysis. The Peto odds ratio (OR), weighted mean differences and 95% confidence intervals (95% CI) were calculated. RESULTS: The overall quality of studies was poor (mean, 2.4/7). Major complications did not differ significantly between closed versus open technique (OR, 0.65; 95% CI, 0.15 to 2.92. Technical failures and difficulties were significantly higher in the closed group, i.e., OR 4.33 (95% CI, 1.96 to 9.56) and OR 4.19 (95% CI, 2.842 to 6.19), respectively. Accuracy of closed and open DPL was comparable with no difference in false-negative or false-positive rates between the two techniques. Procedure time was consistently lower in the closed technique. CONCLUSIONS: The closed DPL technique is comparable to the standard open DPL technique in terms of accuracy and major complications. The advantage of reduced time to perform the closed DPL is offset by the increased technical difficulties and failures of this group. Therefore, any significant benefit of routine closed DPL in improving outcomes can be excluded with more confidence based on pooled data than by the individual trials alone.

Early measurement of systemic lipid peroxidation products in the plasma of major blunt trauma patients.

We sought evidence of oxidant-induced biological membrane damage in 43 resuscitated blunt trauma patients (average ISS, 36.9) within 2-6 hours of injury and before anaesthesia and surgery. The plasma levels of the lipid peroxidation products (conjugated dienes, CDs A 233 nm) and malondialdehyde (MDA, nMol/ml) and the oxidant-inducing effect of the trauma plasma on normal FMLP-stimulated neutrophils were compared to those of control subjects. No differences were observed in the plasma levels of MDA (1.73 +/- 2.15 vs. 1.45 +/- 0.70 nMol/ml) and CDs (2.07 +/- 2.16 vs. 1.28 +/- 0.60 A 233nm), or on stimulated neutrophil superoxide production (26.4 +/- 6.9 vs. 29.0 +/- 6.2 nMol O2-/2 x 10(6) PMNs). These observations persisted when the patients were analyzed based on injury severity, the presence of long bone fractures, and the class of shock at presentation. We conclude that there is no evidence of oxidant-induced membrane damage manifested by increased plasma levels of CDs or MDA within 2 to 6 hours of blunt injury.

Autopsies and death certification in deaths due to blunt trauma: what are we missing?

OBJECTIVES: To determine the frequency, body region and severity of injuries missed by the clinical team in patients who die of blunt trauma, and to examine the accuracy of the cause of death as recorded on death certificates. DESIGN: A retrospective review. SETTING: London Health Sciences Centre, London, Ont. PATIENTS: One hundred and eight deaths due to blunt trauma occurring during the period Apr. 1, 1991, to Mar. 31, 1997. Two groups were considered: clinically significant missed injuries were identified by comparing patient charts only (group 1) and more detailed injury lists from the autopsies and charts of the patients (group 2). OUTCOME MEASURES: Chart and autopsy findings. RESULTS: Of the 108 patients, 78 (72%) were male, and they had a median age of 39 years (range from 2 to 90 years). The most common cause of death was neurologic injury (27%), followed by sepsis (17%) and hemorrhage (15%). There was disagreement between the treating physicians and the causes of death listed on the death certificate in 40% of cases and with the coroner in 7% of cases. Seventy-seven clinically significant injuries were missed in 51 (47%) of the 108 patient deaths. Injuries were missed in 29% of inhospital deaths and 100% of emergency department deaths. Abdominal and head injuries accounted for 43% and 34% of the missed injuries, respectively. CONCLUSIONS: The information contained on the death certificate can be misleading. Health care planners utilizing this data may draw inaccurate conclusions regarding causes of death, which may have an impact on trauma system development. Missed injuries continue to be a concern in the management of patients with major blunt trauma.

The pneumatic antishock garment: use in experimental acute cardiac tamponade.

Acute cardiac tamponade was created in a large animal model in an effort to investigate the hemodynamic and oxygen transport variables during the inflation of the pneumatic antishock garment (PASG) to two different pressures (60 and 80 mm Hg). Inflation of PASG to either pressure under these conditions had no significant effects on filing pressures to the right or left heart, cardiac index, arterial blood gases, oxygen delivery, indexed pulmonary, and systemic vascular resistances. We conclude in this animal model of acute cardiac tamponade that no beneficial or harmful effects were demonstrated during the application and inflation of the pneumatic antishock garment to 60 or 80 mm Hg.

Experimental gram-negative pneumonia produces a hyperdynamic septic profile.

General anesthesia (GA) and extensive surgery undertaken to reproduce a hyperdynamic septic shock syndrome (HSSS) may confound the observed effects of pure HSSS. A large animal model of HSSS without GA or surgery was created in sheep following production of a Pseudomonas pneumonia by direct bronchoscopic instillation into a dependent lobe using only light ketamine anesthesia. Cardiac output rose significantly (5.05 to 6.32 L/min) while SVR [1,421.4 to 1,000.5 dynes X s X cm(-5)] and mean BP (92.5 to 82.0 mmHg) fell in the septic animals. Systemic infection was confirmed by blood culture. This model reliably produces hyperdynamic sepsis without the confounding effects of GA or extensive surgery.

PMN superoxide radical production following a metabolic-endocrine simulation of trauma.

Serious infections following major trauma remain inexplicably high. Metabolic and endocrine changes after injury have been suggested as being responsible for many of the documented defects in the polymorphonucleocyte (PMN). The in vitro bactericidal activity of normal human PMNs has been examined in this laboratory by assaying the activity of the PMN membrane bound enzyme NADPH oxidase and hence O2- production of the PMN in a metabolic/endocrine milieu designed to simulate moderately severe trauma. This was accomplished by incubating the PMN with physiological and trauma serum concentrations of insulin, glucose, cortisol, epinephrine, and glucagon. The results indicate that the O2- production of the PMN is significantly enhanced in this environment. It would appear that exogenous glucose alone was responsible for this enhanced O2- production.

Effect on cardiopulmonary changes of gram-negative endotoxemia in sheep after type-specific, cross-reactive, and nonspecific immune stimulation.

The purpose of this study was to examine the effects of prior nonspecific immune stimulation (BCG), cross-reactive immunization (E coli J5 0111 whole cells [J5 WC], and core glycolipid [J5 CGL]), and type-specific immunization (Serratia marcescens core glycolipid [SM CGL]) on the cardiopulmonary variables and white blood cell counts of awake, monitored sheep following IV Serratia marcescens endotoxin. Comparison of cardiac output, pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, alveolar-arterial oxygen gradients, and total white blood cells lead us to conclude that type-specific immunization (SM CGL) most effectively ameliorates the changes of gram-negative endotoxemia contrasted to nonimmunization. Core glycolipid cross-reactive (J5 CGL) immunization was somewhat more effective than whole-cell cross-reactive (J5 WC) immunization in this regard. Nonspecific immune stimulation (BCG) was able only to significantly decrease the changes in pulmonary vascular resistance compared to nonimmunization.

Delayed intestinal perforation after nonpenetrating abdominal trauma.

The incidence of hollow-organ injury has increased steadily since the use of seat-belts was introduced. It has become apparent that the clinical manifestations of intestinal injury may be delayed considerably. Delayed perforations can pose a diagnostic challenge to the attending surgeon. The authors report four patients who suffered delayed intestinal perforation 6 or more days after sustaining nonpenetrating abdominal trauma in motor vehicle accidents while wearing passive seat-belt restraints. All patients had low severity of injury (scores ranging from 4 to 13) but had persistent vague abdominal pain before perforation occurred. Three of the four patients suffered spinal trauma as their major initial injury. Such patients appear to be at higher risk for delayed perforation and should be monitored carefully.

Comparison of regional pulmonary perfusion in lobar pneumonia during high frequency and conventional mechanical ventilation in sheep.

We compared the effects of high frequency jet ventilation (HFV), conventional ventilation (CMV), and spontaneous breathing (SB) on regional pulmonary blood flows (QLLL), standard cardiopulmonary measurements and the serum levels of the first generation metabolites of prostacyclin (6-keto-PGF1 alpha) and thromboxane A2 (TxB2) in established left lower lobe pseudomonas aeruginosa pneumonia in 11 sheep. Gram negative pneumonia resulted in significant increases in alveolar-arterial oxygen gradients [(A-a)DO2] and pulmonary shunt fractions (Qs/Qt), as well as a significant decrease in QLLL during SB. Significant differences in standard haemodynamics, (A-a)DO2, Qs/Qt, and QLLL were not observed when HFV was compared to CMV. However, serum levels of 6-keto-PGF1 alpha were elevated when the animals underwent HFV. We conclude that HFV is a safe and efficient method of oxygenation and ventilation in unilobar gram negative pneumonia and also results in a significant increase in the serum levels of 6-keto-PGF1 alpha when compared to CMV in sheep. The exact significance of the latter finding is the subject of current investigation.