Transfusion-associated hazards: A revisit of their presentation.

As a therapy or a support to other therapies, despite being largely beneficial to patients in general, transfusion it is not devoid of some risks. In a moderate number of cases, patients may manifest adverse reactions, otherwise referred to as transfusion-associated hazards (TAHs). The latest French 2016 haemovigilance report indicates that 93% of TAHs are minor (grade 1), 5.5% are moderate (grade 2) and 1.6% are severe (grade 3), with only five deaths (grade 4) being attributed to transfusion with relative certainty (imputability of level [or grade] 1 to 3). Health-care providers need to be well aware of the benefits and potential risks (to best evaluate and discuss the benefit-risk ratio), how to prevent TAHs, the overall costs and the availability of alternative therapeutic options. In high-income countries, most blood establishments (BEs) and hospital blood banks (HBBs) have developed tools for reporting and analysing at least severe transfusion reactions. With nearly two decades of haemovigilance, transfusion reaction databases should be quite informative, though there are four main caveats that prevent it from being fully efficient: (ai) reporting is mainly declarative and is thus barely exhaustive even in countries where it is mandatory by law; (aii) it is often difficult to differentiate between the different complications related to transfusion, diseases, comorbidities and other types of therapies in patients suffering from debilitating conditions; (aiii) there is a lack of consistency in the definitions used to describe and report some transfusion reactions, their severity and their likelihood of being related to transfusion; and (aiv) it is difficult to assess the imputability of a particular BC given to a patient who has previously received many BCs over a relatively short period of time. When compiling all available information published so far, it appears that TAHs can be analysed using different approaches: (bi) their pathophysiological nature; (bii) their severity; (biii) the onset scheme; (biv) a quality assessment (preventable or non-preventable); (bv) their impact on ongoing therapy. Moreover, TAHs can be reported either in a non-integrative or in an integrative way; in the latter case, presentation may also differ when issued by a blood establishment or a treating ward. At some point, a recapitulative document would be useful to gain a better understanding of TAHs in order to decrease their occurrence and severity and allow decision makers to determine action plans: this is what this review attempts to make. This review attempts to merge the different aspects, with a focus on the hospital side, i.e., how the most frequent TAHs can be avoided or mitigated.

Resistive Index or color-Doppler semi-quantitative evaluation of renal perfusion by inexperienced physicians: results of a pilot study.

BACKGROUND: Doppler-based renal resistive index (RI) calculation may help in the early detection of acute kidney injury (AKI). Its feasibility and reproducibility by inexperienced operators remain unknown. The main objective of this study was to compare performances of junior and senior operators in assessing renal perfusion using both the semiquantitative color-Doppler scale and RI calculation. METHODS: Prospective cohort study performed in 3 ICUs. Inexperienced juniors physicians attended a half-day course on renal perfusion assessment using RI calculation and color-Doppler (from 0, absence of renal perfusion; to 3, renal vessels identifiable in the entire field of view). Junior and senior operators used both methods in 69 mechanically ventilated patients, in blind fashion. RESULTS: Failure to obtain RI occurred for a junior operator in a single patient. RI and color-Doppler semi-quantitative values obtained by operators were correlated (r²=0.64 and r²=0.61, respectively). Systematic bias across operators as assessed using Bland-Altman plots was negligible (-0.001 and -0.29, respectively), although precision was limited (95% confidence intervals, +0.105 to -0.107 and +0.98 to -1.04, respectively). RI calculation and semi-quantitative assessment performed well for diagnosing persistent AKI (area under the receiver-operating characteristic curve, 0.84 [95% confidence interval, 0.73-0.97] and 0.87 [0.77-0.97], respectively). CONCLUSION: A brief course on renal Doppler allowed inexperienced operators to assess effectively renal perfusion with a good reliability when compared to senior operators. In addition, our results suggest the good diagnostic performance of both Doppler-based RI and semi-quantitative renal perfusion assessment in predicting short-term renal dysfunction reversibility.

[Dosage adjustment of vancomycin in continuous infusion in critically ill-patients]. / Ajustement de la posologie de la vancomycine administrée en perfusion continue chez des patients de réanimation.

INTRODUCTION: As the susceptibility of staphylococcal strains to glycopeptides rises, it is becoming necessary to increase vancomycin dosages. OBJECTIVE: To evaluate an administration protocol for vancomycin using continuous infusion with a loading dose of 30 mg/kg followed by 30 mg/kg per 24h in intensive care patients presenting creatinine clearance (CLc) greater than 50. RESULTS: A total of 22 patients were included in the study. Serum vancomycin concentrations after 24h (C24h) ranged from 25 to 30 mg/l in seven of 14 patients with CLc less than 120 ml/min (50 %), compared with three patients (21 %) with C24h greater than 35 mg/l and four patients (29 %) with C24 h less than 25 mg/l. However, C24h was less than 20mg/l for the eight patients with CLc greater or equal to 120 ml/min. Bacteriological data was available for eight of the 14 patients with CLc less than 120 ml/min, and in these eight patients, the C24h/MIC was greater or equal to 8; seven of these patients had an AUC/MIC greater or equal to 350. CONCLUSION: Assay of serum vancomycin concentrations after 24h of treatment is necessary to enable rapid adjustment of vancomycin concentration in order to improve therapeutic efficacy or avoid nephrotoxicity.

Short term effect of recombinant tissue plasminogen activator in patients with hemodynamically stable acute pulmonary embolism: results of a meta-analysis involving 464 patients.

UNLABELLED: By considering studies where a mixing of patients with and without shock, with or without invasive procedure, treated with various thrombolytic agents through different ways of infusion, have been included, current meta-analyses on thrombolysis efficacy in Pulmonary embolism (PE) are of limited value. Modern management of PE includes the use of both non-invasive diagnostic methods and intravenous rt-PA as thrombolytic agent. METHODS: We performed a meta-analysis of all randomized trials comparing rt-PA with heparin in patients with hemodynamically stable pulmonary embolism. Only the events clearly identified as related with the venous thromboembolic disease or with the treatment were considered. RESULTS: Five studies involving 464 patients were included. The pooled estimate from all the trials revealed a non-statistically significant reduction in death related to PE or pulmonary recurrence for rt-PA compared with heparin (3.5% versus 4.6%; RR 0.97, 95% CI 0.38 to 2.51, P for heterogeneity among the studies=0.73). Compared with heparin, rt-PA was not associated with a significant increase in major bleeding (4.9% versus 4.6%; RR 0.94, 95% CI 0.39 to 2.27). Similar results were found when only studies including patients with echocardiographic evidence of right ventricular dysfunction were considered. CONCLUSION: Neither mortality due to pulmonary embolism nor objective pulmonary embolism recurrence are decreased by rt-PA compared with heparin in patients with hemodynamically stable pulmonary embolism. No benefit is suggested in studies including patients with right ventricular dysfunction alone.

Evaluation of colonisation of peripheral venous catheters inserted by prehospital emergency service teams (SMUR) in France.

There are no data in the literature on colonisation of peripheral venous catheters (PVCs) inserted by French prehospital emergency and resuscitation service teams (SMUR). In a descriptive and prospective study we evaluated colonisation of PVCs inserted and managed solely by a SMUR team. A total of 171 PVCs were analysed. Bacteriological results were positive for seven catheters (4.09%/threshold=10(2)cfu/mL). Our analyses of the characteristics of patients and interventions show a significantly higher number of elderly patients among those colonised (P=0.02) with less satisfactory venous access (P=0.006) and smaller catheter bores (P=0.009). No differences were seen regarding the other evaluation criteria: gender, aetiology, site of intervention, number and site of venepuncture procedures, blood pressure and duration of catheterisation. The absolute value of colonisation seen in our study appears consistent with those reported in the literature, but no comparisons are possible due to widely divergent catheterisation times between published work (days) and our own data (minutes). Our results suggest a reassessment of current recommendations of routine changeover of these catheters, with the attendant discomfort for patients and cost in terms of time and money. We recommend a randomised study comparing catheter colonisation levels associated with routine catheter replacement with targeted replacement based on risk factors.

[A case of delayed fat embolism after a vertebral osteosynthesis]. / A propos d'un cas d'embolie graisseuse pulmonaire différée post-ostéosynthèse vertébrale.

A 37-year-old woman presented an acute respiratory distress syndrome six days after a post-traumatic vertebral osteosynthesis. First, a pulmonary embolism was suspected, and a thrombolysis realised. This diagnosis was secondary excluded, and the diagnosis of probable fatty embolism was established by the bronchoalveolar lavage. So, this case shows a delayed presentation of fatty embolism and permits a discussion about clinical presentation, and diagnosis methods of such pathology.

Impact of restricting fluoroquinolone prescription on bacterial resistance in an intensive care unit.

The purpose of this study was to assess the effect of reducing prescription of fluoroquinolones in an intensive care unit (ICU) upon bacterial resistance, particularly as regards Pseudomonas aeruginosa. For six months between January 2001 and June 2001, administration of fluoroquinolones was kept to a minimum. A bacteriological screening of patients was performed to assess the incidence of fluoroquinolone-resistant bacteria. There was a 75.8% restriction in prescriptions of fluoroquinolones. There was no significant change in bacterial ecology between the periods preceding (12 months) and following (12 months) restriction. There was a significant recovery of sensitivity of P. aeruginosa to ciprofloxacin (P

[Multiple actinomycosis brain abscesses]. / Abcès cérébraux multiples à Actinomyces.

BACKGROUND: Actinomycosis is a subacute or chronic bacterial infection, which can affect immunocompetent or immunodeficient subjects. It most often occurs in cervico-facial or thoracic-abdominal locations. Central nervous system infection is rare but of severe prognosis. CASE REPORT: A 56 year-old woman with no history of immunodepression was admitted with unexplained fever, inappropriate behaviour, and spatial and temporal disorientation. The progressive worsening of the neurological signs let to coma and mechanical ventilation was required. Brain imaging showed multilocation cerebral abscesses. Stereotaxial biopsy permitted diagnosis of actinomycosis. Patient's outcome was favourable following appropriate dual antibiotherapy without surgical exeresis. DISCUSSION: When lacking bacteriologic identification, diagnosis of cerebral actinomycosis is performed by pathologic findings. Dual antibiotherapy allows full recover, even in the case of multilocation cerebral abscesses.

[Epidemic outbreaks control involving Staphylococcus aureus with reduced sensitivity to glycopeptides]. / Contrôle de phénomènes épidémiques dus à des souches de Staphylococcus aureus de sensibilité diminuée aux glycopeptides.

This study describes two epidemic outbreaks involving Staphylococcus aureus with reduced sensitivity to glycopeptides, one in 2000 involving eight patients and the other in 2001-2002 involving 16 patients. These strains were detected rapidly, thanks to routine screening for the offending organisms in the bacteriology laboratory of our hospital. The clonal character of these strains was confirmed by pulsed field electrophoresis. The management of these epidemic outbreaks confirmed (i) the need for systematic adoption of standard precautions, (ii) the importance of circulating information in combating multi-resistant bacteria, as well as the difficulties in transferring colonised patients to different hospital wards, and (iii) the intermittent nature of S. aureus carriage, resulting in a need for prolonged surveillance of colonised and/or infected patients. In addition, our study underlines the value of a multi-disciplinary approach to the management of diffusion of multi-resistant bacteria.

Older people included in a venous thrombo-embolism clinical trial: a patients' viewpoint.

BACKGROUND AND OBJECTIVES: despite the numerous publications debating ethical rules of clinical research, older patients' opinions are rarely taken into account. We report on the feelings and memories related by older patients included in a randomised controlled trial. DESIGN AND SETTINGS: a closed-questionnaire was submitted to patients, aged >65 years, who had been included in the randomised trial "PREPIC". PREPIC was a multicentre open trial performed in France, that included 400 patients over 42 months. The aim of PREPIC was to evaluate the benefits and risks of prophylactic filter placement in patients with proximal deep-vein thrombosis who were considered to be at risk for pulmonary embolism. RESULTS: 104 patients (mean age: 74 years) were interviewed. At the time the trial was proposed to them, 45% of patients felt surprised or shocked and 30% feared incurring additional risks. While 85% of patients did not remember the trial methods (including the randomisation), most older patients (77%) not only judged that they received clear medical information but also well remembered (95%) the aim of the study and the treatment they received (67%). Finally, most older patients not only did not regret their participation (91%), but would also recommend their close relations to participate in a clinical trial (62%). CONCLUSIONS: this study demonstrates that medical scientific information can be understood and remembered by older people.

Death of terminally ill patients on a stretcher in the emergency department: a French speciality?

OBJECTIVES: To determine the frequency, modalities of admission and management of terminally ill patients who died on a stretcher in an emergency department (ED). DESIGN AND SETTING: Retrospective study in an ED of a university hospital. METHODS: Current place of residence, modalities of admission in ED, mortality probability scores and type of management were extracted for each patient in the terminal stage of chronic disease who died on a stretcher in our ED during a 3year period. RESULTS: Of 159 deaths observed in the ED, 56 (35%) concerned terminally ill patients. The illness was a malignancy in 22 cases, a neurological disease in 22 cases and a cardiopulmonary disease in 12 cases. Most of the patients were referred by their regular doctor. Seventy-two percent of the malignancy patients were living at home, 55% of the neurological patients came from nursing facilities and 58% of the cardio-respiratory patients came from the hospital. In 73%, 83% and 23% of the patients with malignancy, cardiopulmonary and neurological diseases, respectively, admission was related to the evolution of the chronic disease. Severity of illness on admission was similar whatever the disease. Request for compassionate end-of-life care was expressed in only 12.5%. At the ED, 91% of patients with neurological diseases received palliative support care. Supportive therapy was undertaken in one third of patients with malignancy or cardiopulmonary disease. CONCLUSION: An ED may be used as a place for dying for some terminally ill patients. This could be related to the legal opposition to withdrawal or withholding of life-support therapies as well as the absence of guidelines from scientific bodies.

The oxygenation variations related to prone positioning during mechanical ventilation: a clinical comparison between ARDS and non-ARDS hypoxemic patients.

OBJECTIVES: To compare, in clinical practice, the oxygenation variations related to prone positioning (PP) during mechanical ventilation in ARDS and non-ARDS hypoxemic patients. DESIGN AND SETTING: Prospective observational study of data on consecutive patients treated with the same protocol in the intensive care unit (ICU) of a university hospital. PATIENTS: From May 1996 to December 1998, 226 PP periods without adjunction of nitric oxide (NO) inhalation and/or almitrine bismesylate infusion, performed in 59 mechanically ventilated hypoxemic patients (arterial oxygen tension/fractional inspired oxygen (PaO2/FIO2) ratio <300 mmHg) with no evidence of left ventricular failure, were included in this study. MEASUREMENTS: Arterial blood gas was measured before the PP, at 1 h from the beginning of the PP, at the end of the PP and 1 h after returning to the supine position. RESULTS: We analyzed 136 PP periods in 34 non-ARDS patients (60.2%) and 90 in 25 ARDS patients. The PP was repeated and the duration of the PP periods was: 10.6+/-0.22 h. The PP during the mechanical ventilation appeared to be safe and well tolerated. A PaO2/FIO2 ratio improvement at the end of the PP period, occurred for 196 periods (86.7%) with a mean PaO2/FIO2 ratio increase of +46.4+/-0.03% at the end of the PP periods compared to the baseline supine value. The PaO2/FIO2 ratio variations at 1 h after the start of the PP, at the end of the PP period and at 1 h after the return to supine were not different in ARDS or non-ARDS hypoxemic patients. The PaO2/FIO2 ratio improvement appeared to be more intense and more rapid in ARDS patients. CONCLUSIONS: In about 90% of periods, PP improved the PaO2/FIO2 ratio in patients with ARDS as well as in hypoxemic patients with non-ARDS. Studies are necessary to determine the impact of PP on survival and the mechanical ventilation duration in ARDS or non-ARDS hypoxemic patients.

Prospective study of nosocomial colonization and infection due to Pseudomonas aeruginosa in mechanically ventilated patients.

OBJECTIVE: To investigate the respective contribution of endogenous and exogenous transmission of Pseudomonas aeruginosa in the colonization of lungs in the mechanically ventilated patient, to estimate the role of P. aeruginosa colonization in the occurrence of severe infections, and to extrapolate appropriate control measures for the prevention of P. aeruginosa ventilator-associated pneumonia. DESIGN: Prospective study of the presence of P. aeruginosa (in stomach fluid, throat specimens, stool, and sputum) on admission, twice a week throughout the patient's stay, and in their environment. O-serotyping, pulsed-field gel electrophoresis, and arbitrarily-primed polymerase chain reaction were used to characterize the strains. SETTING: The two intensive care units (ICUs 1 and 2) of a university hospital. PATIENTS: During a 6-month period, 59 patients were included (21 in ICU 1 and 38 in ICU 2). RESULTS: P. aeruginosa was isolated in 26 patients, including ten pneumonia cases and seven colonizations on admission. The incidence of acquired colonization was statistically different between the two ICUs: 5.5 and 20.5 per 1000 days of mechanical ventilation, in ICUs 1 and 2, respectively. Endogenous acquisition was the main origin of P. aeruginosa colonization (21 of 26 patients) and the upper respiratory tract was the main bacterial reservoir in broncho-pulmonary colonization and infection. However, during the 6-month period of the study, a multidrug-resistant strain of P. aeruginosa O:11, isolated in the sink of the room of 12 patients, was found responsible for two colonizations (1 digestive, 1 throat/lungs) and one pneumonia. As a whole, from 26 cases of colonization/infection with P. aeruginosa, 5 were related to an exogenous contamination (environmental reservoir in 4 patients and cross-contamination in one patient). CONCLUSIONS: These results emphasize the need for applying various infection control measures to prevent colonization of patients with P. aeruginosa, including strategies to limit the potential of sinks from acting as a source or reservoir for this bacterium.

Serum and ascitic procalcitonin levels in cirrhotic patients with spontaneous bacterial peritonitis: diagnostic value and relationship to pro-inflammatory cytokines.

OBJECTIVE: To assess the potential role of procalcitonin and pro-inflammatory cytokines, TNF-alpha, and IL-6, in the diagnosis of spontaneous bacterial peritonitis (SBP). DESIGN: Prospective study. SETTING: The emergency unit of a teaching hospital. PATIENTS: We included 21 patients with SBP and 40 patients with sterile ascitic fluid. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the diagnosis of SBP, the best markers were serum levels of procalcitonin with a cut-off value of 0.75 ng/ml, a sensitivity of 95%, a specificity of 98%, and ascitic fluid levels of IL-6 with a cut-off value of 5,000 ng/ml, a sensitivity of 100%, and a specificity of 88%. C-reactive protein and serum polymorphonuclear count have low sensitivity/specificity at 62/92% and 57/90%, respectively. From 21 patients with SBP, ascitic fluid to serum ratio of TNF-alpha and IL-6 was greater than to 2 in all cases with a mean at 6.2 +/- 6.5 and 34 +/- 31, respectively. By contrast, this ratio for procalcitonin was less than 1 in all cases with a mean at 0.31 +/- 0.25. We found no correlation between procalcitonin levels and cytokine levels in either ascitic fluid or serum. CONCLUSIONS: Serum procalcitonin level may become a useful marker for the diagnosis of SBP in cirrhotic patients. The low ratio of ascitic fluid to serum procalcitonin supports the hypothesis that procalcitonin is not produced intraperitoneally.

Endotoxaemia in patients with severe sepsis or septic shock.

OBJECTIVE: To examine the incidence and the bacteriological and clinical significance of endotoxaemia in ICU patients with severe sepsis or septic shock. DESIGN: Prospective review. SETTING: A 15-bed general ICU in a university hospital. PATIENTS: One hundred sixteen patients hospitalised in our ICU fulfilling Bone's criteria for severe sepsis or septic shock and with an available early endotoxin assay (chromogenic limulus assay). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The clinical characteristics of the population were: age 63.6 +/- 11.4 years; SAPS II: 45.4 +/- 15.6; mechanical ventilation: 72.4%; septic shock: 51.7% (n = 60); bacteraemia: 28.4% (n = 33); gram-negative bacteria (GNB) infection 47.4% (n = 55); ICU mortality: 39.6% (n = 46). Detectable endotoxin occurred in 61 patients (51.2%; mean level: 310 +/- 810 pg/ml). There was no relationship between detectable endotoxin and severity of infection at the moment of the assay. Endotoxaemia was associated with a higher incidence of bacteraemia (39.3% vs 16.3%; p = 0.01). There was a trend (p = 0.09) towards an association between positive endotoxin and gram-negative bacteraemia or GNB infection but this was non-significant. This relationship became significant only in the case of bacteraemia associated with GNB infection irrespective of the site of infection. CONCLUSION: Early detection of endotoxaemia appeared to be associated with GNB infection only in cases of bacteraemic GNB infection. Early endotoxaemia correlated neither to occurrence of organ dysfunction nor mortality in patients with severe sepsis or septic shock. This study suggests that the use of endotoxaemia as a diagnostic or a prognostic marker in daily practice remains difficult.

[Bepridil: importance of serum level in treatment surveillance]. / Bépridil: intérêt du dosage sérique dans la surveillance du traitement.

OBJECTIVE: Despite precise recommendations for prescription and monitoring, tosades de pointes is still observed with bepridil. The purpose of this study was to demonstrate the contribution of bepridil serum assay in therapeutic supervision. PATIENTS AND METHODS: Seventy-five patients over 70 years of age were included. Prolongation of the QT interval was observed in 23 patients. RESULTS: The potential prognostic factors for increased QT interval as demonstrated by univariate logistic regression were hypokaliemia, bradycardia, renal failure and bepridil serum level. After multivariate logistic regression, the persisting causal factors for increased QT interval were hypokaliemia, bradycardia and bepridil serum level. CONCLUSION: Prolongation of the QT interval remains dependent on several variables. Bepridil determination during treatment is insufficient alone.

[Rapid diagnosis of the type of meningitis (bacterial or viral) by the assay of serum procalcitonin]. / Diagnostic rapide du type de méningite (bactérienne ou virale) par le dosage de la procalcitonine sérique.

OBJECTIVE: It has been shown that serum procalcitonin (PCT) can be used to differentiate bacterial from viral meningitis in children in all cases. The aim of this study was to demonstrate the interest of PCT in the management of suspected meningitis in adults. PATIENTS AND METHODS: We conducted a prospective study including 179 consecutive patients admitted to the emergency department for suspected meningitis. All samples were taken at patient admission. The discriminant potential between bacterial and viral meningitis was studied for cerebrospinal fluid parameters (cytology, protein, glucose, lactate) and serum parameters (C reactive protein, PCT). RESULTS: Thirty-two patients had bacterial meningitis, 90 had viral meningitis and meningitis was ruled out in 57. Among all studied parameters, the most discriminant for distinguishing between bacterial and viral meningitis in 100% of the cases proved to be serum procalcitonin with a threshold value of 0.93 ng/ml. CONCLUSION: Serum procalcitonin is an interesting parameter in the emergency department for management of meningitis suspicion in adults.

High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis.

It was shown in children that serum procalcitonin was the best marker to use to differentiate bacterial from viral meningitis. To evaluate procalcitonin in the diagnosis of acute bacterial and viral meningitis, we conducted a prospective study including adult patients who were suspected of having meningitis and who were admitted to an emergency department. Cerebrospinal fluid (CSF) and serum levels of procalcitonin were measured in 105 consecutive patients. The diagnosis of meningitis was based on clinical findings, gram staining, culture, and chemical analysis of CSF. Twenty-three patients had bacterial meningitis, 57 had viral meningitis, and 25 did not have meningitis. Bacteriologic and chemical analysis of CSF did not allow correct differentiation of viral from bacterial meningitis. On the other hand, a serum procalcitonin level >0.2 ng/mL had a sensitivity and specificity of up to 100% in the diagnosis of bacterial meningitis. Serum procalcitonin levels seem to be the best marker in differentiating between bacterial and viral meningitis in adults.

ICAM-1 and CD11b inhibition worsen outcome in rats with E. coli pneumonia.

We investigated whether inhibiting an endothelial adhesion molecule [intracellular adhesion molecule 1 (ICAM-1)] would alter outcome and lung injury in a similar fashion to inhibition of a leukocyte adhesion molecule (integrin CD11b) in a rat model of gram-negative pneumonia. Inhibition of ICAM-1 with monoclonal antibody (MAb) 1A29 (1 mg/kg sc or 0.2 or 2 mg/kg iv, q 12 h x 3) or of CD11b with MAb 1B6 (1 mg/kg sc, q 12 h x 3) were compared against similarly administered placebo proteins in rats challenged with intrabronchial Escherichia coli. After challenge, all animals were treated with antibiotics. ICAM-1 MAb (6 mg/kg, iv, total dose) increased mortality vs. control (P = 0.03). CD11b MAb (3 mg/kg, sc, total dose) did not significantly (P = 0.16) increase mortality rates, but this was not in a range of probability to exclude a harmful effect. All other doses of MAb had no significant effect on survival rates. ICAM-1 and CD11b MAbs had significantly different effects on the time course of lung injury, circulating white cells and lymphocytes, and lung lavage white cells and neutrophils (P = 0.04-0.003). CD11b MAb decreased, whereas ICAM-1 MAb increased these measures compared with control from 6 to 12 h after E. coli. However, from 144 to 168 h after E. coli both MAbs increased these measures compared with control rats but to a greater level with CD11b MAb. Thus both ICAM-1 and CD11b appear to be necessary for survival during E. coli pneumonia. Although these adhesion molecules may participate differently in early lung injury, with CD11b increasing and ICAM-1 decreasing inflammation and injury, both are important for the resolution of later injury. During gram-negative pneumonia the protective roles of ICAM-1 and CD11b may make their therapeutic inhibition difficult.