[Postpartum haemorrhage: recommendations for clinical practice by the CNGOF (December 2004)].
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Anesthesia↗
Biomedical subjects
A Mignon
Publications and source records attributed to A Mignon.
[Prophylaxis of thromboembolic complications in obstetrics and gynaecology].
Venous thromboembolism is a leading cause of maternal mortality in many countries, including France. Most enquiries have repeatedly demonstrated that many deaths could be avoided, suggesting the need to update and ensure a wider diffusion of recommendations. Although thromboembolism-induced maternal death plays a major role, the absolute incidence of events remains low, reducing the ability to perform well-designed research and the level of recommendations presented. Many personal or pregnancy-related factors have been identified as increasing the risk of thromboembolism in pregnant patients but few of them have been associated with a significantly increased risk. A history of thromboembolic event and some thrombophilic factors (including antithrombin deficiency and antiphospholipid syndrome) carry the greatest risk. Pregnancy itself, caesarean delivery and the postpartum period, although associated with an increased risk play a minor role when not combined with other risk factors. Prophylactic treatment relies mainly on low molecular weight heparins which safety is now well established in pregnant patients. Dose and duration of treatment should be adapted to the perceived level of risk. The occurrence of a thromboembolic event is also increased after gynaecological surgery but major and cancer surgery carry the greatest risk. Here also, low molecular weight heparins play a leading role, although non pharmacologic means are useful. Dose and duration should be dependent on the level of risk.
Adult↗
[Indications for labile blood products and the physiology of transfusion in surgery].
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Adolescent↗
[There are still contraindications to the use of epidural anaesthesia in obstetrics].
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Anesthesia, Epidural↗
[Magnesium sulfate in obstetrics: current data].
OBJECTIVE: To review the available evidence regarding history, pharmacology, physiology, maternal/fetal side effects, and efficacy of magnesium sulfate in pregnant women. DATA SOURCES: The literature in Medline was searched from 1966 through April 2003 using the terms "magnesium sulfate," "tocolytic," "preeclampsia," "eclampsia," and "pregnancy." Reviews of bibliographies of retrieved articles provided additional references. RESULTS: Magnesium sulfate (MgSO4) has long been used for prophylaxis of preterm delivery (tocolytic affect) and eclampsia prophylaxis (neuroprotective effect). Randomized controlled trials and systematic reviews have demonstrated the efficacy of magnesium sulfate in preventing eclampsia in patients with preeclampsia or in patients with eclampsia. Whether magnesium sulfate should be administered to patients with severe preeclampsia or to mild preeclampsia is discussed in the manuscript. Inversely, it appears that magnesium sulfate is ineffective in delaying birth or preventing preterm birth when it is used as a tocolytic. Furthermore, there is evidence that high cumulative doses of magnesium sulfate may be associated with increased infant mortality. CONCLUSION: The evidence to date confirms the efficacy of magnesium sulfate therapy for women with eclampsia and preeclampsia. However, magnesium sulfate should not be used in order to treat preterm labor.
Adult↗
[Initial management of primary postpartum hemorrhage].
Accurate management of primary postpartum hemorrhage requires perfect knowledge of a recent protocol accessible at all times. Staff members and equipment need to be adjusted to the emergency situation. The first step is to establish a rapid diagnosis. This could be done with collecting bags, placed immediately after the birth. Once the diagnosis has been established, it has to be communicated to the whole team including obstetricians, midwives and anesthetists. A search for the cause of the hemorrhage is premordial. Abdominal uterine palpation confirms the diagnosis of uterine atony, the most frequent cause of postpartum hemorrhage. Two management schemes are possible depending on whether or not there is retention of the placenta. When the placenta is retained, manual removal has to be performed to empty the uterine cavity and to rule out uterine rupture. After placental delivery, manual control of the uterine cavity is always required. Uterine massage has to be performed after the intrauterine manoeuvres and must not be stopped too quickly. Rapidly other origins can be excluded: episiotomy or low genital tract lacerations requiring rapid repair, coagulation disorders requiring specialised care, or hematomas. During the same time, uterotonic drugs have to be used. Oxytocin (intravenous injection of 5 to 10 IU) is generally employed. Prostaglandins cannot be proposed as publications reporting their efficiency are not validated. Meanwhile, the anesthetists will have begun the first measures of resuscitation.
Decision Trees↗
[Anesthesiologists at the initial stage of postpartum hemorrhage].
Adequate management of postpartum hemorrhage (PPH) requires, after early recognition, four components undertaken simultaneously: communication, resuscitation, monitoring, investigating the cause of bleeding, arresting the bleeding. Early recognition of PPH relies on either a perceived or a quantified blood loss of 500-1000 ml and over (using a collecting bag), or the presence of clinical signs of shock (hypotension, tachycardia, tachypnea, altered mental status). Precise timing of the diagnosis of PPH must be must annotated. Once the diagnosis is established, appropriate senior professionals, including the anesthesiologist at the early stage, must be called in. The cornerstones of initial resuscitation are restoration of blood volume and oxygen carrying capacity, achieved, with adequate intravenous access, initially with cristalloids, followed by colloids, associated with oxygen by face mask. Initial resuscitation is performed and its efficiency is assessed by continuous monitoring, hemoglobin bedside tests (Hemocue), full blood count and clotting screen. Oxytocine (Syntocinon) efficacy and side-effects are evaluated by anesthesiologists. Adequate anesthetic technique must be performed to permit to the obstetricians to perform a diagnostic procedure (manual removal of placenta, uterine revision), and to most frequently obtain arrest of bleeding. Hemodynamic stability is required for loco-regional anesthesia, while on the other hand, general anesthesia with crush induction and intubation will be performed. Anesthesiologists must anticipate in case of failure of initial measures, including in alerting the blood transfusion service and calling for additional help.
Anesthesia, Obstetrical↗
Hepatic response to sepsis: interaction between coagulation and inflammatory processes.
OBJECTIVES: a) To review the hepatic response to sepsis and to establish how this response contributes to coagulation and inflammatory processes; b) to review the physiologic and biochemical mechanisms that suggest hepatic dysfunction may occur during sepsis, enhance procoagulant and proinflammatory activities, and participate in the potential evolution to multiple organ dysfunction syndrome. DATA SOURCES: A summary of published medical literature from MEDLINE search files and published reviews on liver function in experimental and human sepsis. DATA SUMMARY: In sepsis, the liver plays a major role in host defense mechanisms. Kupffer cells are responsible for bacterial scavenging, bacterial products inactivation, and inflammatory mediators clearance and production. Hepatocytes, via receptors for many proinflammatory cytokines, modify their metabolic pathway toward gluconeogenesis, amino-acid uptake, and increased synthesis of coagulant and complement factors and protease inhibitors. The acute-phase protein (APP) response also contributes to the procoagulant state, especially by enhancing the inhibition of protein C (alpha1-antitrypsin and alpha2-macroglobulin) and by decreasing liver synthesis of protein C and antithrombin (negative APPs). Elevated C-reactive protein levels (positive APPs) promote the expression of tissue factor by mononuclear cells. Increased liver production of thrombin-activatable fibrinolytic inhibitor (positive APPs) enhances fibrinolysis inhibition. Conversely, such hepatic inflammatory and coagulation processes in sepsis may alter the function of this organ. Indeed, the liver can be injured by activated Kupffer cells that release chemokines, attract blood neutrophils into the liver, and activate them. Neutrophils up-regulate their surface adhesion molecules, tissue factor, and Kupffer cells, whereas tissue factor pathway inhibitor and thrombomodulin are almost undetectable in endothelial cells. This may lead to microcirculatory disturbances, fibrin deposition, hepatocyte injury, endotoxin and bacteria spillover, and multiple organ failure. CONCLUSIONS: In sepsis, the liver participates in host defense and tissue repair through hepatic cell cross-talk that controls most of the coagulation and inflammatory processes. When this control is not adequate, a secondary hepatic dysfunction may occur and may sometimes lead to bacterial products spillover, enhanced procoagulant and inflammatory processes, and in turn, multiple organ failure and death.
Acute-Phase Proteins↗
Control of apoptosis: therapeutic implications.
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Animals↗
Therapeutic liver repopulation in a mouse model of hypercholesterolemia.
Liver repopulation constitutes an attractive approach for the treatment of liver disorders or of diseases requiring abundant secretion of an active protein. We have described previously a model of selective repopulation of a normal liver by Fas/CD95-resistant hepatocytes, in which we achieved up to 16% hepatocyte repopulation. In the present study, we investigated the therapeutic efficacy of this strategy. With this aim, apolipoprotein E (ApoE) knockout mice were transplanted with Fas/CD95-resistant hepatocytes which constitutively express ApoE. Transplanted mice were submitted to weekly injections of non-lethal doses of the Fas agonist antibody Jo2. After 8 weeks of treatment, we obtained up to 30% of the normal level of plasma ApoE. ApoE secretion was accompanied by a drastic and significant decrease in total plasma cholesterol, which even fell to normal levels. Moreover, this secretion was sufficient to markedly reduce the progression of atherosclerosis. These results demonstrate the efficacy of this repopulation approach for correcting a deficiency in a protein secreted by the liver.
Animals↗
Ischemic spinal cord injury induced by aortic cross-clamping: prevention by riluzole.
OBJECTIVE: Recent studies confirmed the deleterious role of glutamate in the pathophysiology of spinal cord ischemia induced by aortic cross-clamping. We investigated the effect of riluzole, an anti-glutamate drug, in a rat model of spinal cord ischemia. MATERIALS AND METHODS: Spinal cord ischemia was induced in normothermia for 14 min in Sprague-Dawley rats using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation (n=15), control (n=15) receiving only vehicle, riluzole (n=15) receiving riluzole (4 mg/kg) before clamping and at the onset of reperfusion. Separate animals were used for monitoring physiologic parameters in the sham-operation (n=3), control (n=5), and riluzole (n=5) groups. Neurologic status was assessed at 6, 24 h, and then daily up to 96 h. Rats were randomly killed at 24, 48, or 96 h (n=5 for each time). Spinal cords were harvested for histopathology, immunohistochemistry for microtubule-associated protein 2 (MAP-2), TUNEL staining, and analysis of DNA fragmentation by agarose gel electrophoresis. RESULTS: All sham-operated rats had a normal neurologic outcome, whereas all control rats suffered severe and definitive paraplegia. Riluzole-treated rats had significantly better neurologic function compared to the control. Histopathology disclosed severe neuronal necrosis in the lumbar gray matter of control rats, whereas riluzole-treated rats suffered usually mild to moderate injury. Riluzole particularly prevented motor neurons injury. MAP-2 immunoreactivity was completely lost in control rats, whereas it was preserved either completely or partly in riluzole-treated rats. TUNEL staining revealed numerous apoptotic neurons scattered within the whole gray matter of control rats. Riluzole prevented or dramatically attenuated apoptotic neuronal death in treated rats. DNA extracted from lumbar spinal cords of sham-operated and riluzole-treated rats exhibited no laddering, whereas spinal cords from control rats showed DNA laddering with fragmentation into approximately 180 multiples of base pairs. CONCLUSIONS: Riluzole may protect the spinal cord in a setting of severe ischemia by preventing neuronal necrosis and apoptosis. This drug may therefore be considered for clinical use during 'high risk' surgical procedures on the thoracoabdominal aorta.
Animals↗
[Mupirocin: its use].
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Anti-Bacterial Agents↗
Paradoxical inhibition of c-myc-induced carcinogenesis by Bcl-2 in transgenic mice.
Here, we investigated changes in apoptosis during tumor progression by analyzing the effect of coexpressing various antiapoptotic genes on the multistage process of c-myc-induced hepatocarcinogenesis in transgenic mice. Whereas continuous c-myc gene overexpression in the liver led to cellular hepatocarcinoma, the coexpression of the bcl-2 gene inhibited the emergence of liver tumors, by inhibiting a pretumoral phase characterized by increased proliferation and apoptosis. This antioncogenic effect was specific to Bcl-2 and was not shared by other antiapoptotic genes such as bcl-xL and a dominant negative form of p53. Thus, we have shown that Bcl-2 can have a tumor suppressor effect in vivo on c-myc-induced hepatocarcinogenesis during the emergence of neoplastic foci.
Animals↗
Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study.
CONTEXT: Tumor necrosis factor alpha (TNF-alpha) is believed to be a cytokine central to pathogenesis of septic shock. TNF2, a polymorphism within the TNF-alpha gene promoter, has been associated with enhanced TNF-alpha production and negative outcome in some severe infections. OBJECTIVES: To investigate the frequency of the TNF2 allele in patients with septic shock and to determine whether the allele is associated with the occurrence and outcome of septic shock. DESIGN: Multicenter case-control study conducted from March 1996 to June 1997. SETTING: Seven medical intensive care units in university hospitals. SUBJECTS: Eighty-nine patients with septic shock and 87 healthy unrelated blood donors. MAIN OUTCOME MEASURES: Frequency of the TNF2 allele among patients with septic shock and among those who died and the level of corresponding TNF-alpha concentrations. RESULTS: Mortality among patients with septic shock was 54%, consistent with the predicted mortality from the Simplified Acute Physiologic Score (SAPS II) value. The polymorphism frequencies of the controls and the patients with septic shock differed only at the TNF2 allele (39% vs 18% in the septic shock and control groups, respectively, P =.002). Among the septic shock patients, TNF2 polymorphism frequency was significantly greater among those who had died (52% vs 24% in the survival group, P =.008). Concentrations of TNF-alpha were higher in 68% and 52% with the TNF2 and TNF1 polymorphisms, respectively, but their median values (48 pg/mL vs 29 pg/mL) were not statistically different (P = .31). After controlling for age and the probability of death, derived by the SAPS II score, multiple logistic regression analysis showed that, for the same rank of SAPS II value, patients with the TNF2 allele had a 3.7-fold risk of death (95% confidence interval, 1.37-10.24). CONCLUSION: The TNF2 allele is strongly associated with susceptibility to septic shock and death due to septic shock.
Alleles↗
Growth hormone prevents human monocytic cells from Fas-mediated apoptosis by up-regulating Bcl-2 expression.
Apoptosis and particularly Fas-mediated apoptosis has been proposed to play a key role in controlling monocyte homeostasis. We and others have documented the regulatory function of human growth hormone (hGH) on monocytic cells, which prompted us to investigate the role of hGH on their response to Fas antigen cross-linking. Using human promonocytic U937 cells constitutively producing hGH upon gene transfer and human primary monocytes cultured in the presence of recombinant hGH, we demonstrated that hGH diminished Fas-mediated cell death by enhancing the expression of the antiapoptotic oncoprotein Bcl-2 as well as the level of bcl-2alpha mRNA. In parallel, we established that overexpression of Bcl-2 through gene transfer into normal U937 cells also diminished Fas-induced apoptosis. Further, as a result of Bcl-2 overexpression, we found that hGH greatly depressed Fas-induced activation of the cysteine protease caspase-3 (CPP32), which in turn affected the cleavage of poly(ADP-ribose) polymerase. Altogether, these data provide evidence that hGH mediates its protective effect through a Bcl-2-dependent pathway, clearly a crucial step in enhanced survival of monocytic cells exposed to Fas-induced death.
Apoptosis↗
Adenoviral gene therapy of the Tay-Sachs disease in hexosaminidase A-deficient knock-out mice.
The severe neurodegenerative disorder, Tays-Sachs disease, is caused by a beta-hexosaminidase alpha-subunit deficiency which prevents the formation of lysosomal heterodimeric alpha-beta enzyme, hexosaminidase A (HexA). No treatment is available for this fatal disease; however, gene therapy could represent a therapeutic approach. We previously have constructed and characterized, in vitro, adenoviral and retroviral vectors coding for alpha- and beta-subunits of the human beta-hexosaminidases. Here, we have determined the in vivo strategy which leads to the highest HexA activity in the maximum number of tissues in hexA -deficient knock-out mice. We demonstrated that intravenous co-administration of adenoviral vectors coding for both alpha- and beta-subunits, resulting in preferential liver transduction, was essential to obtain the most successful results. Only the supply of both subunits allowed for HexA overexpression leading to massive secretion of the enzyme in serum, and full or partial enzymatic activity restoration in all peripheral tissues tested. The enzymatic correction was likely to be due to direct cellular transduction by adenoviral vectors and/or uptake of secreted HexA by different organs. These results confirmed that the liver was the preferential target organ to deliver a large amount of secreted proteins. In addition, the need to overexpress both subunits of heterodimeric proteins in order to obtain a high level of secretion in animals defective in only one subunit is emphasized. The endogenous non-defective subunit is otherwise limiting.
Adenoviridae↗
Differential protective effects of Bcl-xL and Bcl-2 on apoptotic liver injury in transgenic mice.
Fas ligand (CD95L) and tumor necrosis factor-alpha (TNF-alpha) are pivotal inducers of hepatocyte apoptosis. Uncontrolled activation of these two systems is involved in several forms of liver injury. Although the broad antiapoptotic action of Bcl-2 and Bcl-xL has been clearly established in various apoptotic pathways, their ability to inhibit the Fas/CD95- and TNF-alpha-mediated apoptotic signal has remained controversial. We have demonstrated that the expression of BCL-2 in hepatocytes protects them against Fas-induced fulminant hepatitis in transgenic mice. The present study shows that transgenic mice overexpressing BCL-XL in hepatocytes are also protected from Fas-induced apoptosis in a dose-dependent manner. Bcl-xL and Bcl-2 were protective without any change in the level of endogenous Bcl-xL or Bax and inhibited hepatic caspase-3-like activity. In vivo injection of TNF-alpha caused massive apoptosis and death only when transcription was inhibited. Under these conditions, PK-BCL-XL mice were partially protected from liver injury and death but PK-BCL-2 mice were not. A similar differential protective effect of Bcl-xL and Bcl-2 transgenes was observed when Fas/CD95 was activated and transcription blocked. These results suggest that apoptosis triggered by activation of both Fas/CD95 and TNF-alpha receptors is to some extent counteracted by the transcription-dependent protective effects, which are essential for the antiapoptotic activity of Bcl-2 but not of Bcl-xL. Therefore, Bcl-xL and Bcl-2 appear to have different antiapoptotic effects in the liver whose characterization could facilitate their use to prevent the uncontrolled apoptosis of hepatocytes.
Animals↗
LPS challenge in D-galactosamine-sensitized mice accounts for caspase-dependent fulminant hepatitis, not for septic shock.
Experimental models of sepsis using endotoxin challenges, including studies with sensitized animals with D-galactosamine, have largely contributed to the basic rationale for innovative clinical trials in human septic shock, which have, to date, failed. The ability of these models to reproduce human disease has been highly discussed. We report here that the widely used D-galactosamine/LPS model does not account for septic shock. Treatment with YVAD-CMK, a potent tetrapeptide inhibitor of caspases of the interleukin (IL)-1beta converting enzyme (ICE) family, protects from LPS-induced liver apoptosis and mortality in D-galactosamine-sensitized mice when administered either before or up to 2 h after the lethal challenge. This curative effect is related to complete inhibition of caspase-3 activity in the liver. However, YVAD-CMK does not affect LPS-induced release of IL-1beta and does not protect from a lethal dose of LPS in unsensitized mice. These experiments demonstrate the difference between these two widely recognized experimental models of sepsis. LPS toxicity in D-galactosamine-treated mice, leading to blocked gene transcription, results from tumor necrosis factor (TNF)-alpha-induced caspase-3-dependent liver injury, not from the systemic inflammatory response. These results provide evidence that inhibitors of the ICE caspase family can prevent or even overcome the ongoing hepatic injury induced by TNF-alpha during sepsis, ischemia-reperfusion, or severe hepatitis.
Amino Acid Chloromethyl Ketones↗