Jacques Mangalaboyi

Meningococcemia and purpura fulminans in adults: acute deficiencies of proteins C and S and early treatment with antithrombin III concentrates

It has been recently suggested that an acquired deficiency of proteins C and S could contribute to the pathogenesis of meningococcemic purpura fulminans (PF) in children. Our study was designed to measure the levels of antithrombin III (AT III), protein C, and protein S during adult PF and to determine the effects of an early infusion of high doses of AT III concentrates on clinical and biological alterations of PF. We studied five consecutive adult patients with meningococcemia (type B) and PF. The levels of AT III, protein C (antigen and activity), and protein S (total and free) were measured at admission and 24 h and 1 month later. The treatment included in each case: amoxycillin, dobutamine and high doses of AT III concentrates. All patients survived and were discharged without any sequelae. At admission, biological data were consistent with severely depressed protein C and protein S levels and moderately decreased AT III levels, without any discrepancy between protein C antigen and activity. After 24 h, AT III and protein S levels were within normal ranges, whereas protein C levels were still depressed. These data are consistent with the theory of a particular imbalance in the anticoagulant systems during meningococcemic PF, contrasting with the usual findings observed during septic disseminated intravascular coagulation. The possibility must be considered that high doses of one anticoagulant (AT III concentrates) could compensate for the acute decrease in the other (protein C system).

Cefepime-induced neurotoxicity: an underestimated complication of antibiotherapy in patients with acute renal failure

Abstract Objectives: To describe five new cases of life-threatening cefepime-induced neurotoxicity observed in a 2-year period. Setting: A university intensive care unit. Patients: Five patients recently treated with cefepime, admitted for seizures and coma. All suffered from acute renal failure, induced by sepsis and combined aminoside therapy, or by cefepime itself in one case. Interventions: All patients underwent hemodialysis, which led to complete neurological improvement in four of them. One patient remained comatose and subsequently died. Measurements: Blood and CSF cefepime levels were measured by high performance liquid chromatography before and after hemodialysis. Conclusion: The frequency of cefepime-induced neurotoxicity is probably underestimated. Monitoring of renal function and close neurological survey in treated patients should allow an early diagnosis of this complication. Urgent hemodialysis seems the best therapeutic method to obtain a rapid neurological improvement.

Use of capnography in diagnosis of pulmonary embolism during acute respiratory failure of chronic obstructive pulmonary disease

In chronic obstructive pulmonary disease (COPD) patients, there is a difference between Paco2 and endtidal partial pressure of CO2 (PetCo2). This gradient P(a-et)Co2 is due to ventilation/perfusion mismatching and deadspace, and is usually abolished by forced and prolonged expiration. We hypothesized that this gradient might not be canceled by forced expiration in the case of acute respiratory failure (ARF) related to pulmonary embolism (PE). Forty-four adult COPD patients were prospectively entered into this study; they were suspected of having ARF related to PE on the basis of clinical and biological data on admission. Maximum expired partial pressure of CO2 (Pemco2) was measured in mechanically ventilated and sedated patients by an interrupt of mechanical support. CO2 concentration was recorded during the following prolonged and passive expiration. The test was considered valid if an expiratory plateau was obtained. Pemco2 was measured in triplicate. Simultaneously, Paco2 was measured and the ratio, R = ([1 – Pemco2]/Paco2) × 100, was calculated. Pulmonary angiography was performed on the same day for all patients. Results showed that 17 patients had PE (PE+) and 17 had no PE (PE-). The two groups were comparable regarding mean age, severity of underlying chronic respiratory disease, Paco2, Pao2, and hemodynamic data on admission. P(aem)co2 and R were significantly different in PE+ and PE- patients at 12 ± 6.9 torr compared to 1 ± 2.4 torr and at 28 ± 14.8% compared to 2 ± 6.2% (p < .001), respectively. The positive predictive value of the test was 74%, but the negative predictive value 100% and the specificity was 65%, but sensitivity was 100%. We conclude that this test may be useful to rule out a diagnosis of PE during ARF of COPD patients. (Crit Care Med 1990; 18:353)

Effects of a combined antithrombin III and protein C supplementation in porcine acute endotoxic shock

Antithrombin III (ATIII) and protein C (PC) are major inhibitors of the coagulation cascade and might regulate the cytokine network. We tested the possibility that a combined supplementation using these two inhibitors might have synergistic effects on sepsis-induced disseminated intravascular coagulation and shock. Hemodynamics, coagulation parameters, tumor necrosis factor (TNF) a, and interleukin 6 levels were measured in pigs submitted to a bolus infusion of Escherichia coli endotoxin (lipopolysac-charide). Four groups were studied: control lipopolysaccharide, ATIII (100 IU/kg), PC (50 lU/kg), and ATIII-PC (same doses). The endotoxin infusion resulted in a typical hypokinetic shock with disseminated intravascular coagulation in all animals. Compared with the control group, a significant improvement in mean arterial pressure and systemic vascular resistance was observed in the PC and ATIII-PC groups. The increase in lactate levels was almost completely blunted in the PC group. A significant lesser increase in TNFα levels was observed in the ATIII-PC group. No effects were seen on interleukin 6 levels. Coagulation and fibrinolysis parameters were not improved by ATIII and/or PC, except for a lesser decrease in prothrombin time in the ATIII-PC group. We conclude that in this acute endotoxic model, a combined supplementation using PC and ATIII concentrates has favorable effects on hemodynamic parameters and TNFα levels, independently from the anticoagulant actions of these inhibitors.

Effects of N omega-nitro-L-arginine methyl ester on the endotoxin-induced disseminated intravascular coagulation in porcine septic shock.

OBJECTIVES Nitric oxide is known to prevent platelet aggregation and clot formation. Inhibitors of nitric oxide synthase might promote or enhance endotoxin disseminated intravascular coagulation. The present study was designed to evaluate the effects of the arginine analog, N omega-nitro-L-arginine methyl ester (L-NAME), on the endotoxin-induced disseminated intravascular coagulation in a porcine model of septic shock. DESIGN Prospective, comparative, experimental study. SETTING Laboratory at a large university hospital. SUBJECTS Sixteen female piglets, weighing 20 to 28 kg. INTERVENTIONS Three groups of animals were studied: a control group (n = 6); a lipopolysaccharide (LPS)-treated group (n = 5) receiving Escherichia coli endotoxin (5 micrograms/kg/min over 30 mins); and an LPS + L-NAME group (n = 5) receiving endotoxin and, 1 hr after, a bolus of L-NAME (25 mg/kg). MEASUREMENTS AND MAIN RESULTS Hemodynamic changes, usual coagulation parameters, and plasma concentrations of thrombin-antithrombin complexes, antithrombin III activity (At III), tissue plasminogen activator, plasminogen activator inhibitor type 1, and von Willebrand factor were measured at baseline, and at 30, 60, 90, 120, 180, 240, and 300 mins. After euthanasia or death, lungs and kidneys were withdrawn for histologic study. The extent of microvascular thrombosis was assessed by a semiquantitative disseminated intravascular coagulation score. In both septic endotoxin group, administration of LPS resulted in hemodynamic changes typical of severe septic shock, with disseminated intravascular coagulation and histologic changes characterized by adult respiratory distress syndrome and kidney microthrombosis. L-NAME administration normalized mean arterial pressure with a dramatic increase in systemic vascular resistances and a marked decrease in cardiac index. The changes in usual coagulation parameters, AT III, tissue plasminogen activator, and plasminogen-activator inhibitor type 1 concentrations were not different between both septic groups. However, in the LPS + L-NAME group, thrombin-antithrombin complexes and von Willebrand factor were higher and associated with a higher histologic disseminated intravascular coagulation score. CONCLUSION In this model of endotoxin septic shock, L-NAME administration resulted in histologic and coagulation changes consistent with an increased activation of intravascular coagulation.

Redox status of cytochrome a,a3: a noninvasive indicator of dysoxia in regional hypoxic or ischemic hypoxia.

OBJECTIVE Multiwavelength near infrared (NIR) spectrophotometry can monitor the redox state of cytochrome a,a3 (cyt a,a3) in vivo. Because cyt a,a3 is the most immediate reductant of oxygen, this technique has been proposed to evaluate tissue oxygenation. The purpose of this study was to examine the relationship between cyt a,a3 oxidation level as an indicator of dysoxia and oxygen uptake (VO2) when oxygen delivery (DO2) was progressively lowered in an in situ vascularly isolated hindlimb. DESIGN Prospective, randomized, laboratory study. SETTING University research laboratory. SUBJECTS Fourteen pigs. INTERVENTIONS Measurement of critical values for both VO2 and cyt a,a3 oxidation during ischemic and hypoxic hypoxia. MEASUREMENTS AND MAIN RESULTS The right hindlimb of anesthetized, paralyzed, and ventilated pigs was subjected to progressive ischemic or hypoxic hypoxia for 100 mins by ten stepwise decreases in DO2. In ischemic hypoxia (n = 7), arterial inflow (Q) from a pump-membrane oxygenator system was lowered from 50 to 0 mL/min, with PaO2 maintained at 100 mm Hg. In hypoxic hypoxia (n = 6), PaO2 was lowered from 100 mm Hg to 0 mm Hg. Hindlimb DO2 was calculated as the product of Q and arterial oxygen content, and VO2 as the product of Q and arteriovenous difference. The cyt a,a3 oxidation level was measured every 10 secs with a four-wavelength spectrophotometer. These parameters were measured 9 mins after each change of DO2. Critical values for both VO2 and cyt a,a3 oxidation level as a function of DO2 were determined in each animal by dual linear regression analysis. In ischemic and hypoxic hypoxia, a strong correlation was found between cyt a,a3 oxidation level and VO2 in both ischemic and hypoxic hypoxia (r2 =.90 and .87, respectively). Hindlimb vascular resistance increased in ischemic hypoxia and decreased in hypoxic hypoxia when DO2 reached critical DO2. CONCLUSIONS From these results, we concluded that monitoring the cyt a,a3 redox state by NIR spectrophotometry is, in this experimental setting, a sensitive indicator of dysoxia during regional hypoxic or ischemic hypoxia.

Escherichia coli endotoxin reduces cytochrome aa3 redox status in pig skeletal muscle.

ObjectiveTo assess the effect of endotoxin on cytochrome aa3 (C aa3) redox status in a controlled blood flow preparation of pig isolated hindlimb, at a constant oxygen delivery (˙Do2limb) (constant flow period) and during progressive ischemia (decreasing flow period). DesignRandomized, controlled experimental study. SettingUniversity hospital experimental laboratory. SubjectsTen piglets. InterventionsHindlimb blood flow was restricted to the femoral vessels. The arterial femoral blood flow coming from the carotid artery was controlled by a roller occlusive pump. The femoral venous blood flow was returned to the jugular vein. During the first 100 mins, the hindlimb blood flow was maintained at a normal level and then decreased stepwise. Animals were randomized to receive 150 &mgr;g/kg endotoxin lipopolysaccharide (LPS; n = 5) or saline (control; n = 5). Measurements and Main ResultsHindlimb muscle C aa3 redox status was monitored by near-infrared spectroscopy. Hindlimb ˙Do2limb and oxygen consumption (&OV0312;o2limb) were calculated. In the LPS group, a rapid reduction of C aa3 redox status was observed after LPS administration, whereas the hindlimb blood flow remained normal with no change in ˙Do2limb and &OV0312;o2limb. A progressive simultaneous decrease in ˙Do2limb and &OV0312;o2limb was observed during the decreasing flow period with no further reduction in C aa3 redox status. In the control group, no change was observed in C aa3, ˙Do2limb, or &OV0312;o2limb during the constant flow period. During the decreasing flow period, C aa3 redox status was reduced as ˙Do2limb and &OV0312;o2limb decreased. ConclusionOur results suggest that endotoxin may induce a reduction of C aa3 redox status independently of ˙Do2 and &OV0312;o2.

Survival and prognostic factors of allogeneic hematopoietic stem cell transplant recipients admitted to intensive care unit.

Th roughout the course of the disease, patients with hematological malignancies can present life-threatening complications, leading to admission to the intensive care unit (ICU). Th e fi rst studies on this population [1] used to discourage ICU admission for patients with hematological malignancies, particularly when invasive mechanical ventilation (MV) was necessary, with up to 85% ICU mortality rate in that setting [2,3]. However, these early studies mixed diff erent populations of patients, particularly patients with and without allogeneic hematopoietic stem cell transplant (HSCT) [4]. During the last 20 years, the survival of patients with hematological malignancies in the ICU has considerably improved, with the mortality rate reduced to 60%, even for patients needing life-sustaining therapy [5 – 7]. Th is improved survival is the consequence of early admission to the ICU, better cooperation between hematologists and intensive care physicians and the progress of both hematology and intensive care medicine along with a better selection of patients requiring ICU admission. However, allogeneic HSCT recipients still have a very poor prognosis in the ICU, because of the duration of severe neutropenia at early post-transplant stages, the use of immunosuppressive drugs and the occurrence of graft-versus-host disease (GVHD) at later stages [8]. Pulmonary complications are particularly frequent and lead to mechanical ventilation in up to 30% of patients [9]. In specialized centers, survival of allogeneic HSCT recipients in ICUs has slightly improved over recent years, even in cases of mechanical ventilation [10], but only a few studies have focused on this specifi c population. In this study, we retrospectively evaluated, over a period of 10 years, short- and long-term survival, organ failures and prognostic factors for this population admitted to our ICU. All consecutive allogeneic HSCT recipients from our department of hematology admitted to the medical ICU

Carbon dioxide mandatory ventilation (CO2MV): A new method for weaning from mechanical ventilation Description and comparative clinical study with I.M.V. and T. tube method in COPD patient

SummaryWe describe a new technique specially designed for weaning from mechanical ventilation: carbon dioxide mandatory ventilation (CO2MV). CO2MV is based on feedback between end tidal expired partial pressure of carbon dioxide and ventilatory mode, controlled or spontaneous. In order to evaluate its real interest we performed a randomized prospective study, CO2MV vs Intermittent Mandatory Ventilation (IMV) and T. Tube Method (TTM). Fourty-two adult patients with chronic obstructive pulmonary disease entered this study at the end of acute respiratory failure requiring mechanical ventilatory support. We observed a better stability of arterial blood gas during weaning with CO2MV and an increase in success rate (CO2MV 13/14 -IMV 5/14 - TTM 10/14). From this study CO2MV seems available for weaning of COPD patients. Nevertheless, further studies are required to appreciate its real clinical interest.

Pneumatic transport is critical for leukaemic patients with major leukocytosis: what precautions to measure lactate dehydrogenase, potassium and aspartate aminotransferase?

False elevations of plasma lactate dehydrogenase (LDH), potassium and aspartate aminotransferase (AST) have been described, in relation to haemolysis, occurring most often by mechanical release during phlebotomy or specimen processing. We present the cases of two leukaemic patients with severe hyperleukocytosis for whom LDH, potassium and AST were dramatically but falsely elevated. This false elevation was not caused by haemolysis but could be related to white cells lysis during transport through a pneumatic transportation system, enhanced by a specific fragility of leukaemic cells. Interestingly, this interference almost completely disappeared when serum rather than plasma was used, or when leukocytosis came back to normal. This work is meant to alert clinicians to the risks of errors in LDH, potassium and AST in leukaemic patients and suggest what precautions to take.