Karl Byrne

Preventable Complications And Death From Multiple Organ Failure Among Geriatric Trauma Victims

We reviewed 374 consecutive trauma patients over age 65 years to determine (1) if the emergency room Trauma Score (TS) could predict mortality, thereby improving ICU triage, and (2) the frequency of preventable complications in patients who died (n = 31). Fifty-two percent of deaths (n = 16) occurred in patients with TS = 15 or 16. Multiple organ failure/sepsis (MOF/S) was the most common cause of death overall (42%) and was also the most frequent cause of death in patients with a TS = 15-16 (63%). Nonsurvivors in the TS = 15-16 subgroup were older (80.9 +/- 2.0 vs. 74.9 +/- 0.5 years, p less than 0.02) and had greater ISSs (15.8 +/- 3.7 vs. 8.0 +/- 0.4, p = 0.001) than survivors. Patients with a TS less than 15 suffered high overall mortality (45%). Preventable complications contributed to mortality in 32% of all deaths and in 62% of MOF/S deaths. Aggressive care to prevent avoidable complications may improve survival in elderly trauma victims.

Ibuprofen attenuates hypochlorous acid production from neutrophils in porcine acute lung injury

UNLABELLED Hypochlorous acid (HOCl), a neutrophil-generated oxidant, has been implicated in tissue destruction in sepsis-induced acute lung injury (ALI). Ibuprofen, a cyclooxygenase inhibitor, successfully attenuates many of the physiological derangements in ALI. The aim of this study was to examine the role of PMN hypochlorous acid in sepsis-induced ALI and evaluate the effect of ibuprofen therapy. Neutrophils from three groups of young (15-25 kg), anesthetized swine were studied: controls (C, n = 7) received 0.9% NaCl, septic animals (Ps, n = 8) received live Pseudomonas aeruginosa (5 x 10(8) CFU/ml at 0.3 ml/20 kg/min) for 60 min, and ibuprofen-treated animals (Ps + I, n = 6) received Ps plus ibuprofen 12.5 mg/kg administered at 0 and 120 min. Neutrophils were isolated from peripheral blood at 0, 60, and 300 min and the rate and total production of HOCl were assessed on the basis of the ability of the amino acid taurine to trap HOCl. RESULTS Septic (Ps) PMNs produce 32% more HOCl, P less than 0.01, at 300 min than at baseline which was associated with a marked increase in both extravascular lung water (6.44 +/- 0.8 ml/kg, t = 0 vs 16.03 +/- 2.6 ml/kg, t = 300, P less than 0.01) and bronchoalveolar protein content (115 +/- 13 micrograms/ml, t = 0 vs 633 +/- 104 micrograms/ml, t = 300, P less than 0.01). Ibuprofen significantly attenuated (P less than 0.05) HOCl production when compared to Ps, in conjunction with significantly (P less than 0.05) reduced levels of extravascular lung water and bronchoalveolar lavage protein.

Delayed cyclo-oxygenase blockade reduces the neutrophil respiratory burst and plasma tumor necrosis factor levels in sepsis-induced acute lung injury.

Ibuprofen pretreatment attenuates the enhanced neutrophil (PMN) respiratory burst and reduces increased plasma tumor necrosis factor (TNF) activity in porcine sepsis-induced acute lung injury (ALI). These septic responses have been linked to increased alveolar-capillary membrane (ACM) permeability. This study was designed to establish whether delayed ibuprofen treatment would have the same effect and to examine the relationship between PMN oxidant generation and TNF. Three groups of anesthetized, ventilated pigs (15-25 kg) were used. Group Ps received Pseudomonas aeruginosa (5 x 10(8) CFU/mL at 0.3 mL/20 kg/min) for one hour IV; The control group (Con) received 0.9% NaCl. Group D-Ibu received ibuprofen 12.5 mg/kg as a delayed bolus at 30 minutes and again at 120 minutes after Ps. Protein (BAL-P, microgram/mL) in harvested bronchoalveolar lavage fluid and extravascular lung water (EVLW, mL/kg) were used to estimate the integrity of the ACM. Superoxide anion (O2-) generation (ferricytochrome c reduction) from circulating PMNs and plasma TNF activity (L929 fibroblast bioassay) were measured. The EVLW increased significantly (p less than 0.05), as did BAL-P (p less than 0.01), in the P. aeruginosa-treated animals at 300 minutes. These increases were abolished in Group D-Ibu: EVLW, 6.6 +/- 1.0 baseline vs. 14.6 +/- 2.6 Ps 300 vs. 6.8 +/- 0.9 D-Ibu 300; BAL-P, 175 +/- 28 baseline vs. 984 +/- 186 Ps 300 vs. 284 +/- 42.8 D-Ibu 300. Both enhanced PMN oxidant activity and increased plasma TNF activity were significantly attenuated by delayed ibuprofen treatment. These data support the efficacy of the nonsteroidal anti-inflammatory drug, ibuprofen, when used after the onset of a septic stimulus.

Increased morbidity with increased pulmonary albumin flux in sepsis-related adult respiratory distress syndrome

ObjectiveTo determine the feasibility of utilizing a scintigraphic technique to differentiate patients with adult respiratory distress syndrome due to sepsis syndrome from control volunteers and patients with congestive heart failure. Gamma scintigraphy was compared with chest roentgenograms to predict mortality rate and morbidity in adult respiratory distress syndrome (ARDS) patients. DesignProspective study. SettingUniversity hospital ICUs. PatientsThirty-five control volunteers, 19 patients with congestive heart failure, 30 patients with a diagnosis of sepsis. Measurements and Main ResultsAll patients were infused iv with technetium 99m-labeled albumin and underwent computerized gamma-scintigraphic analysis with a portable gamma camera. Lung-to-heart ratio of tracer was calculated and expressed as the slope index. Increase in slope index indicated increased pulmonary albumin flux. Slope index was no different in controls compared with congestive heart failure patients, unless the pulmonary artery occlusion pressure (PAOP) was >30 mm Hg. Patients with a diagnosis of sepsis had an overall increased slope index compared with the other groups. A subgroup of patients in the septic group had a normal slope index. Septic patients with an increased slope index had a significantly (p < .01) longer duration of mechanical ventilation (36 ± 5 vs. 7 ± 1 days), spent longer in the ICU (67 ± 9 vs. 11 ± 1 days), and had a longer hospital stay (113 ± 20 vs. 35 ± 5 days) than septic patients with a normal slope index. ConclusionsGamma scintigraphy successfully differentiated between control volunteers and patients with congestive heart failure with PAOP <30 mm Hg from patients with sepsis-induced ARDS. Although all of the patients with a clinical diagnosis of septic ARDS had similar impairments in oxygenation and chest roentgenograms, those patients with a significantly increased pulmonary albumin flux (>2 SD above control mean) had a markedly increased morbidity. (Crit Care Med 1992; 20:28)

GANGRENOUS STREPTOCOCCAL MYOSITIS: CASE REPORT

Streptococcal infection of the large skeletal muscles is a rare but often rapidly fatal condition that may occur for no apparent reason. Nonsteroidal anti-inflammatory drugs may have an adverse effect on outcome. A high index of suspicion is the key to early diagnosis.

Platelet-activating factor in porcine Pseudomonas acute lung injury

We investigated the role of platelet-activating factor (PAF) in acute septic lung injury by examining the effects of the selective PAF antagonist SRI 63-675 and by measuring PAF in lung tissue in the porcine model. Four groups of pigs (15-25 kg) were studied: saline control (C, n = 5); Pseudomonas (Ps, n = 9), given 5 x 10(8) CFU/ml at 0.3 ml/20 kg/min intravenously over 1 hr; SRI (n = 3), given SRI 63-675 in a 40 mg/kg bolus; and SRI + Ps (n = 5). Ps infusion produced a fulminant lung injury characterized by a threefold increase in pulmonary arterial pressure at 30 min and persistent pulmonary hypertension (P less than 0.05 vs C), a significant (P less than 0.05 vs C) decrease in arterial oxygen tension (PaO2) from 60 min, a significant (P less than 0.05 vs C) increase in extravascular lung water (EVLW) from 120 min, and a significant (P less than 0.05 vs C) increase in albumin flux determined scintigraphically as slope index at 150-180 min. Systemic arterial pressure and cardiac index (CI) decreased significantly (P less than 0.05) in the Ps group vs C at 60 and 180 min, respectively. Bolus injection of SRI 63-675 at the time of Ps infusion blocked the early pulmonary hypertension, attenuated the early and late fall in PaO2, ameliorated the increase in EVLW, and prevented the late (150-180 min) increase in albumin flux. SRI 63-675 had minimal effects on Ps-induced hypotension or alterations in CI.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased survival time after delayed histamine and prostaglandin blockade in a porcine model of severe sepsis induced lung injury

A combination of cimetidine, diphenhydramine, and ibuprofen has been shown to be an effective treatment in a porcine model of septic acute lung injury. The present study was designed to evaluate this therapy in a delayed treatment survival model. Three groups of animals were studied: a control group (C, n = 6) received a sham infusion of 0.9% saline; a septic group (Ps, n = 5) received a continuous infusion of live Pseudomonas aeruginosa organisms; and a treatment group (CID, n = 6) received P. aeruginosa plus cimetidine 150 mg, ibuprofen 12.5 mg/kg, and diphenhydramine 10 mg/kg given at 90 min after P. aeruginosa infusion, and hourly thereafter. Group Ps developed fulminant acute lung injury and hypodynamic septic shock. CID therapy ameliorated temporarily the progressive course of hypoxemia and increased extravascular lung water (EVLW), delayed the onset of cardiovascular deterioration, and improved significantly survival time. It was concluded that CID therapy given at 90 min after the onset of lethal continuous P. aeruginosa infusion improved significantly animal survival time by improving temporarily hypoxemia and increase in EVLW and delaying cardiovascular collapse.

Histamine receptor antagonists, cyclooxygenase blockade, and tumor necrosis factor during acute septic insult

Tumor necrosis factor (TNF) may be a major endogenous mediator of sepsis-induced acute organ injury. We proposed that treatment of septic pigs with the combined agents ibuprofen, a cycloox-ygenase inhibitor, and histamine receptor antagonists, cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) would result in lower circulating levels of TNF and decreased parameters of sepsis-induced injury in these animals. To test this, plasma TNF activity, cardiac index, systemic and pulmonary arterial pressures, arterial Po2 and bronchoalveolar lavage protein content were monitored for 300 min in four groups of anesthetized pigs: saline-infused control pigs (n = 4); pigs infused for 60 min with Pseudomonas aeruginosa (5 x 1088 organisms/mL, .3 mL/20 kg/min) (n = 5) and pigs infused for 60 min with P. aeruginosa plus ibuprofen (12.5 mg/kg) alone (n = 4) or ibuprofen plus cimetidine (150 mg) and diphenhydramine (30 mg/kg) at 0 and 120 min (CID, n = 4). Within 60 min, pigs infused with P. aeruginosa exhibited increased plasma TNF activity (>8-fold increase in ng/mL TNF; L929 cytolysis assay) and showed alterations in all hemodynamic and pulmonary parameters. Ibuprofen or CID administration in the septic pigs decreased peak TNF activity by 4.6 and 10.2 ng/mL, respectively, and CID treatment was correlated with better attenuation of certain sepsis-induced alterations. These results show that CID treatment attenuates sepsis-induced injury and that this is correlated with reduced plasma TNF activity in a porcine model of sepsis-induced acute organ injury.

Ibuprofen prevents deterioration in static transpulmonary compliance and transalveolar protein flux in septic porcine acute lung injury.

UNLABELLED The effects of intravenous ibuprofen on measurements of pulmonary function and alveolar capillary membrane permeability to protein in sepsis-induced porcine acute lung injury (ALI) were studied. Young swine (15-25 kg) were anesthetized, cannulated, and ventilated (5 cm H2O PEEP, 0.5 FIO2, and 15 cc/kg tidal volume). Three groups were studied: septic animals (Ps, n = 10) received Pseudomonas aeruginosa for 1 hr IV, controls (C, n = 9) received 0.9% NaCl, and ibuprofen-treated septic animals (Ps + Ibu, n = 7) received ibuprofen 12.5 mg/kg at 0 and 120 min post Ps. Systemic (SAP) and pulmonary (PAP) arterial pressures, PaO2, cardiac index (CI), static lung compliance (CL), EVLW (thermal cardiogreen), and peripheral white blood cell counts (WBC) were measured. Bronchoalveolar lavage (BAL) was performed for protein and % neutrophil (%PMN) content. RESULTS Ps produced significant (p less than 0.05) decreases in CL, PaO2, SAP, CI, and peripheral WBC and increases in PAP, EVLW, BAL protein, and %PMNs vs. controls. Ibu prevented the early increase in PAP and attenuated the late increase in PAP and EVLW. Ibu also maintained PaO2, CL, BAL protein, and %PMNs in BAL at control levels, but exhibited no significant effect on peripheral leukopenia. These data strongly suggest that ibuprofen administered before and at 120 min after onset of Pseudomonas infusion improves lung compliance and affects neutrophil function sufficiently to significantly ameliorate many of the physiologic derangements in acute sepsis.

RANITIDINE COMPARED TO CIMETIDINE IN MULTIAGENT PHARMACOLOGICAL TREATMENT OF PORCINE PSEUDOMONAS ARDS

The effects of two pharmacologically distinct histamine H2 receptor antagonists were studied in combination with ibuprofen (I) and diphenhydramine (D) in a porcine model of septic ARDS. Cimetidine (C) is reported as having direct oxygen radical scavenging abilities and is an inhibitor of cytochrome P-450, whereas ranitidine (R) acts solely by H2 receptor blockade. Four groups were studied: Group Ps (n = 8) received a continuous infusion of live Pseudomonas aeruginosa 5 x 10(8) CFU/ml at 0.3 ml/20kg/min, Group C (n = 6) received a control saline infusion, and the treatment groups received I (12.5 mg/kg) and D (10 mg/kg) in combination with either C (150 mg, CID, n = 6) or R (25 mg, RID, n = 5) given at 20 and 120 minutes after the onset of Ps. Pulmonary (PAP) and systemic (SAP) arterial pressures, cardiac index (CI), PaO2, thermal cardiogreen extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux (slope index, SI) were measured. Ps infusion produced significant (p less than 0.05) cardiovascular collapse, hypoxemia and increased EVLW and SI. Both CID and RID temporarily reversed pulmonary arterial hypertension and maintained PaO2, EVLW, SAP and CI at control levels throughout the study, and significantly improved SI at 180 min. These results suggest that cimetidine and ranitidine act in this combination therapy primarily as H2 receptor antagonists.