Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial.

BACKGROUND: Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available. PATIENTS AND METHODS: Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion. RESULTS: rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism. CONCLUSION: This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.

Gangrene of the perineum.

Fournier's gangrene, an anaerobic necrotizing cellulitis of the infradiaphragmatic soft tissues, is a serious pathologic entity with an unpredictable course. From 1978 to 1991, a total of 24 men (mean age, 57 years; range 27 to 90) were treated for this entity at our institution. Diagnosis prompted immediate institution of multimodal treatment combining triple antibiotics, surgical dissection, debridement, and repeated surgical drainage. Fecal diversion (16 patients), hyperbaric oxygenation, and standard intensive care procedures were widely indicated and performed quasi-systematically. The mean interval between initial symptoms and diagnosis was 7.4 days. Lesions were limited to the perineum in 11 patients but extended to the abdomen, thighs, or loins in the remaining 13. The pathogens were identified in 19 patients, and hemoculture results were positive in 5. A coloproctologic origin was identified in 12 patients and a urogenital origin in 4. In 2 patients, perineal gangrene occurred postoperatively, and no etiology was determined for 6. Six patients died, and 18 patients recovered, without any sequelae. The prognosis is better when the patient is young (less than 60 years old), has clinically localized disease, without systemic involvement, and sterile hemocultures and is managed with colostomy. A thorough workup is mandatory to determine the etiology (locoregional lesion, malignancy, hemopathy, arteritis).

[Transvascular fluid exchange disturbed by capillary injuries]. / Situations où les échanges liquidiens sont perturbs par des lésions capillaries.

Fluid exchange disorders due to capillary lesions are numerous and their extent depends on the underlying disease as well as the capillary structure of the affected organ. The inflammatory cascade, triggered by sepsis or reperfusion injury, is mediated by several humoral mediators and activated blood cells. These include pro-inflammatory cytokines, arachidonic acid, proteases, oxygen free radicals, polymorphonuclears, procoagulant, complement and fibrinolytic system. The interaction between these mediators leads to a loss of endothelial integrity, a loss of basment membrane and a disruption of the interstitial matrix, with wasting of the endothelial cytoskeleton. The alteration in permeability induces transcapillary exudation of water and protein in the interstitial space, leading to organ dysfunction, mainly the lungs and splanchnic organs. Nitric oxyde, by modulating the response of the endothelium to the cellular interaction may protect against capillary injury. Capillary "stress lesions" following microvascular hypertension are the physiological basis of neurogenic or high altitude pulmonary oedema, and overinflation injury from mechanical ventilation. The anatomic specific features of the cerebral capillaries resulted in the well known concept of blood brain barrier with it's changeing morphology. Under the effect of humoral mediators and cellular interactions, the endothelial cells are able, via a calcium-mediated mechanism, to contract and to modify capillary permeability, leading to vasogenic oedema.

[Transfusion of erythrocyte concentrates. An evaluation in anesthesia and intensive care]. / Transfusion de concentrés érythrocytaires. Une évaluation en anesthésie-réanimation.

OBJECTIVE: To assess the relevance of perioperative packed red blood cell (PRBC) transfusion practice at the University Hospital of Nice, compared with information from the consensus conference on red blood cell transfusion, held by the French Society of Anaesthesia and Intensive Care (SFAR) and the National Agency for the Development of Medical Evaluation (ANDEM) in December 1993. STUDY DESIGN: Retrospective case series analysis. PATIENTS: The study included 240 medical files of surgical patients, transfused in 1994 with PRBC, obtained by drawing of lots following a methodology recommended by ANDEM. METHOD: A reference list according to the statement of the consensus conference was designed for the various surgical specialities and the ICU in which PRBC had been transfused. It included the clinical and laboratory criteria which justified the transfusion, as well as the various categories of PRBC (phenotyped, cytomegalovirus negative, leukocyte-depleted, etc). Autotransfused PRBC were also considered. The data collected from the medical files of the 240 patients were compared with the reference list. RESULTS: In 84.6% of patients (203/240), the PRBC transfusion had been decided with reference either only to a haematocrit level below 0.27 or a level between 0.27 and 0.30 associated with clinical evidence of bad tolerance of blood loss, according to the reference list. A lack of compliance with the reference list occurred in 15.4% of patients (37/240), who had been transfused without any reference to a biological criterion. Another non compliance existed in 50% of patients (12/24) transfused with phenotyped PRBC and in 35.3% (6/17) of those transfused with leucocyte-depleted PRBC. An autotransfusion with PRBC had been carried out in 30.4% of patients (75/240). DISCUSSION: These deviations of transfusion practice from the consensus conference statement, which were more pronounced with phenotyped and leucocyte-depleted PRCB than conventional PRBC, resulted in the edition of a report, with an analysis of the causes of deviations and recommendations for all doctors of our institution prescribing blood transfusions. Another evaluation, extended also to the medical specialities of our hospital and including all blood derivates is planned for 1996.

[Epidural anesthesia and prevention of autonomic hyperreflexia in a paraplegic parturient]. / Anesthésie péridurale et prévention de l'hyperréflectivité autonome chez une parturiente paraplégique.

Pregnancy in a patient suffering from high spinal cord lesions is unusual and can lead to serious autonomic hyperreflexia during delivery. Epidural anaesthesia has been suggested as a means of decreasing such a risk. This clinical report presents the case of a paraplegic patient with lesions above the T3 level who had spinal anaesthesia for a Caesarean section. Her first delivery, six years earlier and without spinal anaesthesia was complicated by serious autonomic hyperreflexia with severe hypertension, seizures and inhalation. These symptoms were at first interpreted as eclampsia. For the Caesarean section, spinal anaesthesia using 0.25% bupivacaine in divided doses presented no difficulty, in spite of important lordosis, and permitted the delivery of a newborn with an Apgar score of 10 at one minute. The upper sympathetic level reached (T4-T6) was assessed by the discontinuing of muscular spasticity and contractures elicited by cutaneous stimuli. At the present time, spinal anaesthesia is the best method for preventing autonomic hyperreflexia. General anaesthesia, especially with halothane, is effective, but requires a deeper anaesthesia with the risk of serious hypotension and its possible repercussions on the fetus. Moreover it does not decrease the risk of autonomic hyperreflexia during the postoperative period.

Clinical pharmacology of nicardipine in liver transplant patients.

Slow calcium channel antagonists are widely used among transplanted patients suffering from hypertension, although some of them tend to reduce hepatic blood flow. The aim of our study was to determine the pharmacological properties of nicardipine in transplanted patients with hypertension. Ten hours after liver transplantation, six patients (three men, three women) received 5 mg of intravenous nicardipine to prevent high blood pressure during intensive care. Prior to the administration and during the study (at the completion of the infusion, 3, 5, 10, 15, 20, 30, 45, and 60 min after infusion), the systemic and splanchnic parameters were measured (Swan Ganz catheter). Blood samples were drawn simultaneously from radial artery and free hepatic veins, in order to obtain the hepatic extraction of nicardipine. The hepatic extraction ratio was around 70% for the first 3 min, then decreased and remained stable thereafter, around 45%, showing a non linear first-pass metabolism pattern. Plasma hepatic clearance of nicardipine (699-850 ml/min) was close to total plasma clearance throughout the study (978 +/- 222 ml/min, from 71 to 87%) and half of the estimated hepatic plasma flow values at the same times (1467-1770 ml/min, from 44 to 51%). No statistically significant changes were observed in cardiac output and hepatic blood flow during the study, although there was a decrease in mean arterial blood pressure from 87 +/- 6 mmHg baseline level to 76 +/- 3 mmHg, 60 min after administration. Nicardipine chlorhydrate seems to be appropriate in post operative liver transplant patients when blood pressure must be decreased. Nicardipine safely lowers peripheral resistance, and does not induce changes in hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of the activities and value of allergo-anesthetic consultation at the University Hospital Center of Nice 1985-1991]. / Bilan d'activité et intérêt d'une consultation d'allergo-anesthésie au CHU de Nice de 1985 à 1991.

Life-threatening accident during anesthesia scarcely happen but the consequences may be dramatic. We report our experience of an allergo-anesthesia consultation created since 1985 in Nice hospital. 452 patients have been investigated: 1) 109 for life-threatening anaphylactic and anaphylactoid drug reactions. They have been investigated by: skin tests intradermal reactions (IDR) and prick tests with substances used during anesthesia (drugs and latex) and for all the muscle relaxants; the radioabsorbent test (RAST) for the muscles relaxants, propofol and latex; the human basophilic degranulation test (HBDT) for all the other drugs. We used the imputability decision table to classify the reactions. When anaphylaxis diagnosis was established (14) an "allergy card" was given to patients which identified the drugs to which they had a positive reaction. 62 patients have presented an anaphylaxis: 57 due to muscle relaxants (37 due to suxamethonium), 4 to latex and 1 to a gelatin. Patients were subsequently contacted and 50 of the 58 have responded. 18 of these patients have received 22 new anesthesias. Without exception, the advises to avoid a drug have been followed, 17 patients have a positive reaction to a muscle relaxant. In four of these, another muscle relaxant (skin test negative) was used without any trouble. For the other 13 who had shown a cross reactivity, all the muscle relaxants had been rejected and another anesthetic technique have been used: local anesthesia (3 cases), epidural (2 cases) associated or not with narcotics (propofol, midazolam), general anesthesia (propofol, midazolam, droperidol, phenoperidine). These drugs were all skin test negative.(ABSTRACT TRUNCATED AT 250 WORDS)

[Subacute arsenic poisoning]. / Intoxication suraiguë à l'arsenic.

A cas is reported of a 23-year-old man who voluntarily took a massive dose of arsenic (at least 8 g). In spite of the ingested amount and the acute nature of the poisoning, the patient survived 8 days. Gastrointestinal, neurologic and cardiac features were predominant including nausea, vomiting, choleroid diarrhoea, encephalopathy, peripheral neuropathy, and finally a fatal toxic cardiomyopathy. Metabolic acidosis, moderate cytolysis and an anticoagulant effect were also observed. This unique characteristic was partly due to a circulating anticoagulant with prothrombinase activity, as well as direct antivitamin K activity. Postmortem examination revealed: a congestive oesophagitis; a necrosing gastritis involving all the stomach wall; diffuse hepatic steatosis; skin lesions with vascular congestion and dermoepidermal detachment; discrete subepicardial congestive lesions. Arsenic was found in all tissues.

[Changes in plasma histamine and catecholamines levels after injection of chymopapain in chemonucleolysis]. / Evolution des taux d'histamine et de catécholamines plasmatiques après injection de chymopapaïne lors des chimionucléolyses.

Because pruritus, erythema and tachycardia are observed in some patients during chemonucleolysis, a prospective study was designed to investigate the plasma levels of histamine and catecholamines occurring after an injection of chymopapain. Thirteen patients (11 men and 2 women), mean age 38 +/- 11 years, were studied. They all had negative prick skin tests, human basophil degranulation tests (HBDT) and radio-absorbent tests (RAST) to chymopapain. The patients were premedicated with 100 mg hydroxyzine and 3 g tranexamic acid. Sedation was carried out using 0.1 mg.kg-1 droperidol and 0.02 mg.kg-1 phenoperidine. The nucleosus pulposus was visualized with 3 ml of contrast medium (lopamiron 300); 2 ml of chymopapain were then injected. Blood samples were obtained at T1 (after the contrast medium, but before the chymopapain), and then 5, 10, 15, 20 and 30 minutes after the chymopapain. The usual haemodynamic parameters were recorded at the same times. Four patients had clinical signs (group I), whereas the other nine (group II) did not. There was an increase in histamine levels in three patients from group 1, as well as in two in group II (up to 33 nmol.l-1). However, mean histamine and catecholamines levels were comparable in both groups at all times, and between times, of sampling. There therefore was no relationship between clinical signs and the release of histamine or catecholamines. The premedication with an antihistamine may have protected the patients, but the signs reported by four patients may also be due to the chymopapain itself.

[Energy substrates in parenteral nutrition]. / Apports énergétiques en nutrition parentérale.

The most appropriate nutriment for total parenteral feeding (TPF) must be nutritionally efficient, safe and easy to use. Glucose is the most used carbohydrate as it has most of these qualities, as well as a high rate of metabolism by all tissues. It has not been clearly demonstrated that the administration of exogenous insulin with glucose improves nitrogen retention. Substitutes for glucose, such as fructose, maltose, galactose or polyols (xylitol, surbitol, glycerol) are not really superior to glucose itself. On the other hand, they have major side-effects. Therefore, they are not much used as energy substrates for TPF, at least not for long term TPF. Intravenous fat emulsions have taken an important place as a source of energy during TPF. Fat emulsions containing long chain triglycerides (LCT) supply essential fatty acids (EFA) (linolenic and linoleic acids), thus preventing EFA deficiency. The metabolism of fat emulsions is influenced by various factors: age, metabolic and nutritional status, the amount of glucose intake, insulin deficiency, sepsis, heparin therapy. Recently, medium chain triglycerides (MCT) have been proposed as an alternative energy source. The latter are cleared more rapidly from the blood, and are therefore less liable to be deposited in the liver and adipose tissue; they are also oxidized more quickly and more completely. MCT are safe to use at a rate of less than 0.12 g.kg-1.h-1 and with a MCT/LCT ratio less than 3 to 1. The simultaneous administration of glucose prevents an acceleration of ketogenesis. MCT/LCT emulsions are a safe and effective source of calories. It is important that those patients for whom such nutriment may be of particular interest should be identified. Fat emulsions associated with glucose seem to be more efficient in terms of nitrogen sparing effect than glucose alone. They also avoid the problems due to the infusion of large amounts of glucose (excessive carbon dioxide production, fatty infiltration of the liver), while there is no EFA deficiency. If the infusion of TPF nutriment must be continuous in intensive care patients, or during the postoperative period, cyclic nocturnal parenteral nutrition over a 12 or 16 hour period may be used in patients who are not in a catabolic state, or only mildly so. This is a safe and efficient method of nutritional support, which reduces the incidence rate of TPF-induced cholestasis.

[Comparison of propanidid with propofol for dental surgery of short or medium duration]. / Comparaison propanidide-propofol en chirurgie stomatologique de courte ou moyenne durée.

The properties of propofol in emulsion given by continuous intravenous infusion to spontaneously breathing patients have been well studied. Thirty randomized voluntary premedicated patients undergoing dental extraction were anaesthetized with propofol (2.5 mg X kg-1 IVD, and 9 mg X kg-1 X h-1) or with propanidid (9 mg X kg-1 IVD, and 60 mg X kg-1 X h-1), supplemented with nitrous oxide in oxygen and fentanyl. Induction, maintenance and recovery times had the same characteristics. Highly significant differences occurred between the two groups regarding the increase in heart rate, apnoea and recovery time. This study showed that propofol was an eminently suitable agent for continuous intravenous anaesthesia in spontaneously breathing patients for dental surgery.