Biomedical subjects

Karim Asehnoune

Publications and source records attributed to Karim Asehnoune.

At least 19 recordsLinked to original sources

PubMed2006

beta2-Adrenoceptor blockade partially restores ex vivo TNF production following hemorrhagic shock.

The aim of the study was to assess the mechanisms through which leukocyte deactivation occurs upon hemorrhagic shock. In particular, the influence of beta-adrenergic tone was evaluated. BALB/c mice were hemorrhaged and resuscitated 60 min after hemorrhage. Animals were sacrificed 60 min later by exsanguination. Blood from exsanguination was cultured ex vivo with lipopolysaccharide (LPS) and heat-killed Staphylococcus aureus Cowan I (SAC). Hemorrhage resulted in a major decrease of LPS-induced TNF production whereas IL-10 production was significantly enhanced. Selective beta(2)-adrenoceptor antagonists (ICI 118,551) attenuated the decrease in TNF production and further enhanced IL-10 production. Hemorrhage did not alter SAC-induced TNF production levels whereas IL-10 production was increased. ICI 118,551 further increased the production of both TNF and IL-10. These data suggest that leukocyte deactivation after LPS stimulation is not a generalized phenomenon since TNF production was maintained when another microbial activator was used. IL-10 production was enhanced after hemorrhagic shock, independently of the nature of the triggering agent. Finally, this study demonstrates that beta(2)-adrenoceptor ligands play an important role in blood leukocyte deactivation to LPS after hemorrhagic shock.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed2006

[Propofol to facilitate spinal anesthesia in the lateral position in patients with femoral neck fracture].

PURPOSE: The aim of this study was to assess the feasibility and efficacy of propofol before positioning elderly patients with a femoral neck fracture in the lateral decubitus position, to perform a spinal anesthetic. METHODS: In this prospective and descriptive study, 79 consecutive patients, > 75 yr old, with a femoral neck fracture were included. Propofol, 0.5 mg x kg(-1), was administered. If loss of consciousness was not obtained (Ramsay score < or = 3/6), then additional doses of 0.25 mg x kg(-1) were given until a Ramsay score of 4 or 5 was attained. Then, the patient was turned to the lateral decubitus position, the fractured side up. The efficacy of propofol was assessed by observing a grimace during positioning and asking the patients if they had recall of pain. Hemodynamic data and oxygen saturation were collected. RESULTS: Forty-three patients required a single injection, 34 required two injections and only two patients required three injections. No grimace and no recall of pain were recorded during the study. There was no desaturation (SpO(2) < 92 %), and hypotension, defined as a systolic blood pressure decrease > 30% from baseline, was observed. CONCLUSION: Propofol is a simple and efficacious means of providing comfort while positioning elderly patients with a femoral head fracture before performing spinal anesthesia.

Aged↗

PubMed2006

Spinal anesthesia using single injection small-dose bupivacaine versus continuous catheter injection techniques for surgical repair of hip fracture in elderly patients.

Aging and disease may make elderly patients particularly susceptible to hypotension during spinal anesthesia. We compared the hemodynamic effect of continuous spinal anesthesia (CSA) and small dose single injection spinal anesthesia (SA) regarding the incidence of hypotension. Seventy-four patients aged >75 yr undergoing surgical repair of hip fracture were randomized into 2 groups of 37 patients each. Group CSA received a continuous spinal anesthetic with a titration of 2.5 mg boluses every 15 min of isobaric bupivacaine, while group SA received a single injection spinal anesthetic with 7.5 mg of isobaric bupivacaine. The overall variations in noninvasive automated arterial blood pressure were not statistically significantly different in the 2 groups at baseline and after CSA or SA (not significant). In the SA group, 68% of patients experienced at least one episode of hypotension (decrease in systolic arterial blood pressure greater than 20% of baseline value) versus 31% of patients in the CSA group (P = 0.005). In the SA group, 51% of patients experienced at least one episode of severe hypotension (decrease in systolic arterial blood pressure more than 30% of baseline value) versus 8% of patients in the CSA group (P < 0.0001). In the CSA group, 4.5 +/- 2 mg of ephedrine was injected versus 11 +/- 2 mg in the SA group (P = 0.005). In the CSA group, 5 mg (2.5-10) of anesthetic solution was required versus 7.5 mg in the SA group (P < 0.0001). We conclude that, in elderly patients undergoing hip fracture repair, CSA provides fewer episodes of hypotension and severe hypotension compared with a single intrathecal injection of 7.5 mg bupivacaine.

Aged↗

PubMed2005

Influence of resuscitation volume on blood cells TNF production in a murine model of haemorrhage.

The influence of haemorrhage and resuscitation on Tumour Necrosis Factor (TNF) production by whole blood cultures under endotoxin (Escherichia coli LPS) stimulation was investigated in male BALB/c mice. Haemorrhagic shock was induced by removing 0.026 +/- 0.003 mL of blood/g via a cardiac puncture, resulting in a 50% decrease in arterial pressure and a metabolic adidosis. Animals were resuscitated successfully (normotensive) despite a residual base deficit and hyperlactatemia, 60 min after the haemorrhage by the restitution of shed blood volume (SBV) with or without an additional volume of crystalloid (Lactated Ringer's solution) equal to 50, 100 (isovolumetric resuscitation) or 200% of SBV. Pulmonary failure (hypoxia-hypercarbia) and myocardial injury (troponin I release) was observed in this last group. TNF production by whole blood cultures stimulated ex vivo by LPS was estimated 60 min after the end of resuscitation. Haemorrhage resulted in a 48-60% decrease in TNF production. This decrease so-called 'leukocyte deactivation' was not modified by the restitution of SBV with or without crystalloid except for isovolumetric resuscitation which resulted in the cytokine level returning to control in the absence of clear cardiopulmonary dysfunction. In the present murine model of haemorrhage, modifying resuscitation volume influences in vitro TNF production in whole blood cultures challenged by LPS.

Anesthetics, Inhalation↗

PubMed2005

HMGB1 contributes to the development of acute lung injury after hemorrhage.

High mobility group box 1 (HMGB1) is a novel late mediator of inflammatory responses that contributes to endotoxin-induced acute lung injury and sepsis-associated lethality. Although acute lung injury is a frequent complication of severe blood loss, the contribution of HMGB1 to organ system dysfunction in this setting has not been investigated. In this study, HMGB1 was detected in pulmonary endothelial cells and macrophages under baseline conditions. After hemorrhage, in addition to positively staining endothelial cells and macrophages, neutrophils expressing HMGB1 were present in the lungs. HMGB1 expression in the lung was found to be increased within 4 h of hemorrhage and then remained elevated for more than 72 h after blood loss. Neutrophils appeared to contribute to the increase in posthemorrhage pulmonary HMGB1 expression since no change in lung HMGB1 levels was found after hemorrhage in mice made neutropenic with cyclophosphamide. Plasma concentrations of HMGB1 also increased after hemorrhage. Blockade of HMGB1 by administration of anti-HMGB1 antibodies prevented hemorrhage-induced increases in nuclear translocation of NF-kappa B in the lungs and pulmonary levels of proinflammatory cytokines, including keratinocyte-derived chemokine, IL-6, and IL-1 beta. Similarly, both the accumulation of neutrophils in the lung as well as enhanced lung permeability were reduced when anti-HMGB1 antibodies were injected after hemorrhage. These results demonstrate that hemorrhage results in increased HMGB1 expression in the lungs, primarily through neutrophil sources, and that HMGB1 participates in hemorrhage-induced acute lung injury.

Animals↗

PubMed2005

Involvement of PKCalpha/beta in TLR4 and TLR2 dependent activation of NF-kappaB.

Protein kinase C (PKC)alpha/beta dependent signaling events downstream of TLR4 or TLR2 were investigated in neutrophils stimulated with LPS or PGN. Pretreatment of neutrophils with the structurally distinct PKCalpha/beta inhibitors Go6976 or GF109203X decreased nuclear translocation of NF-kappaB and production of the proinflammatory cytokine TNF-alpha. Inhibition of PKCalpha/beta also prevented LPS or PGN induced phosphorylation of IKKalpha/beta, phosphorylation and degradation of IkappaB-alpha, as well as phosphorylation of the p65 subunit of NF-kappaB. Activation of p38, JNK, and ERK 1/2 in response to TLR2 engagement was diminished in neutrophils in which PKCalpha/beta was inhibited. However, no alteration in the activation of these kinases was found in TLR4 stimulated neutrophils when PKCalpha/beta was blocked. Such results indicate that distinct intracellular signalling pathways leading to MAPK activation are induced by TLR4 and TLR2 stimulation. PKCalpha/beta can regulate NF-kappaB dependent transcription in neutrophils both by enhancing nuclear translocation of NF-kappaB and also by stimulating phosphorylation of the p65 subunit.

Animals↗

PubMed2005

Hydrocortisone increases the sensitivity to alpha1-adrenoceptor stimulation in humans following hemorrhagic shock.

OBJECTIVE: To assess the pressor response to phenylephrine infusion before and after hydrocortisone in severe trauma patients and to correlate this response with their adrenal reserve. DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit in a university teaching hospital. PATIENTS: Twenty-three young trauma patients (Injury Severity Score, 38 +/- 14) were studied at the end of the resuscitative period (27 +/- 15 hrs after trauma). INTERVENTIONS: Total cortisol response to intravenous corticotropin bolus (250 microg) was obtained. Total cortisol response <9 microg/dL defined an impaired adrenal function and the patient was called a nonresponder. Twelve to 24 hrs following this stimulation, phenylephrine was infused in a stepwise manner to establish the phenylephrine-mean arterial pressure dose-response curve before and after intravenous hydrocortisone administration (50 mg). An Emax model was used to describe the curve; the influence of the group (responder/nonresponder), the sequence (before/after hydrocortisone), and three covariates (Injury Severity Score, shock, and interleukin-6) were thereafter tested. MEASUREMENTS AND MAIN RESULTS: Forty-three percent of patients were nonresponders. Total cortisol response was not correlated with serum albumin concentration and was negatively correlated with the interleukin-6 concentration. A trend for a higher incidence of nonresponders (53% vs. 36%) and a lesser total cortisol response (7.9 +/- 5.1 vs. 12.5 +/- 5.1 microg/dL) was observed in the shock patients. A phenylephrine dose-response structure (E0, ED50, and Emax) was described without influence of the group and the sequence. However, hydrocortisone induced a 37% decrease in ED50 without change in Emax in the shock patients. CONCLUSION: An acute administration of hydrocortisone increases the sensitivity to alpha1-adrenoceptor stimulation in fully resuscitated severe trauma patients following hemorrhagic shock. This effect is independent of the adrenal reserve of the patients and different from that previously reported in septic patients.

Adrenergic alpha-1 Receptor Agonists↗

PubMed2005

Early embolization and vasopressor administration for management of life-threatening hemorrhage from pelvic fracture.

BACKGROUND: In this retrospective study, we reviewed our protocol for management of hemodynamically unstable patients with pelvic injury. METHODS: We managed the patients with the same predetermined plan including controlled hemodynamic resuscitation with early use of vasopressors and pelvic angiography as a first-line treatment. RESULTS: Of 311 patients with pelvic fracture, 32 hemodynamically unstable patients (10.3%) underwent pelvic angiography, which was followed by embolization in 25 cases. Angiography was successful for 24 patients (96%) and extrapelvic bleeding was diagnosed in 5 patients (15%). Three of six laparotomies performed before angiography were nontherapeutic. One of seven laparotomies performed after angiography was negative. CONCLUSION: A protocol for management of patients with pelvic injury and hemodynamic instability that is associated with controlled resuscitation including vasopressor and early pelvic angioembolization is effective for treating pelvic hemorrhage and diagnosing extrapelvic hemorrhage. Further studies are needed to confirm the respective place of angiographic and surgical control of bleeding.

Adult↗

PubMed2005

Bupivacaine's action on the carrageenan-induced inflammatory response in mice: cytokine production by leukocytes after ex-vivo stimulation.

We aimed to study the effect of bupivacaine on the systemic response elicited by intraplantar injection of carrageenan. To that purpose, we studied the effects of carrageenan, bupivacaine, or both on the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-10 by whole blood cultured in the presence of lipopolysaccharide (LPS) and of heat-killed Staphylococcus Aureus Cowan (SAC). Mice received a hindpaw injection of carrageenan with or without encapsulated IM bupivacaine given contralaterally. Whole blood was sampled 15 h later and cultured for 24 h with LPS or SAC. The amounts of TNF-alpha, IL-1beta, and IL-10 in the supernatants were measured. In the presence of LPS or SAC, proinflammatory cytokine (TNF-alpha and IL-1beta) production was increased after carrageenan. Bupivacaine prevented this inflammatory response: 992 +/- 102 versus 2146 +/- 338 versus 919 +/- 116 pg/mL for TNF-alpha (bupivacaine + carrageenan versus carrageenan versus control after LPS stimulation). This effect of bupivacaine was less after SAC stimulation. Moreover, IL-10 was not involved in the inhibition of proinflammatory cytokine production observed after treatment by bupivacaine alone. These experiments show that carrageenan-induced hindpaw inflammation modifies the blood cell reactivity to LPS and SAC and that bupivacaine regulates the systemic response elicited by carrageenan. Furthermore, IL-10 does not seem to be a factor of the antiinflammatory response induced by bupivacaine. The precise mechanism underlying this effect of bupivacaine remains to be clarified.

Anesthetics, Local↗

PubMed2005

Small-dose bupivacaine-sufentanil prevents cardiac output modifications after spinal anesthesia.

Spinal injection of small-dose (SD) bupivacaine decreases the likelihood of hypotension compared with large-dose (LD) bupivacaine. We assumed that a SD of bupivacaine could also prevent the decrease in cardiac output (CO). Patients undergoing elective urologic, lower abdominal, or lower limb surgery under spinal anesthesia were included in this prospective randomized study. Spinal injection consisted of 5 mug of sufentanil and either SD (7.5 mg of hyperbaric bupivacaine with glucosemonohydrate 80 mg/mL; n = 19 patients) or LD (12.5 mg of hyperbaric bupivacaine with glucosemonohydrate 80 mg/mL; n = 19 patients). CO (impedance cardiography), arterial blood pressure, and heart rate) were measured at 1 min before performance of spinal block and 2, 10, and 30 min after the intrathecal injection. Sensory level was also assessed at 30 min. CO was higher in the SD group as compared with the LD group from 2 min to 30 min after spinal anesthesia. Moreover, CO increased at 2 min in the SD group and decreased at 10 and 30 min in the LD group compared with baseline value. In conclusion, SD bupivacaine provides successful anesthesia and gives better CO stability than LD.

Adult↗

PubMed2004

Phosphoinositide 3-kinase and Akt occupy central roles in inflammatory responses of Toll-like receptor 2-stimulated neutrophils.

Neutrophils are critical initiators and effectors of the innate immune system and express Toll-like receptor 2 (TLR2) and TLR4. Although signaling through pathways involving phosphoinositide 3-kinase (PI3-K) and the downstream kinase Akt (protein kinase B) plays a central role in modulating neutrophil chemotaxis and superoxide generation in response to engagement of G protein-coupled receptors, the importance of these kinases in affecting inflammatory responses of neutrophils stimulated through TLR2 has not been examined. In these experiments, we found activation of Akt in neutrophils stimulated with the TLR2-specific ligands peptidoglycan and the lipopeptide tri-palmitoyl-S-glyceryl-Cys-Ser-(Lys)(4) that occurred earlier and was of greater magnitude than that present after exposure to the TLR4 agonist LPS. The release of the proinflammatory mediators TNF-alpha and macrophage inflammatory protein-2 was inhibited in a dose-dependent manner by PI3-K blockade. The IC(50) for inhibition of peptidoglycan-stimulated Akt activation and macrophage inflammatory protein-2 release correlated closely, indicating linkage of these two events. PI3-K blockade did not inhibit nuclear translocation of NF-kappa B, but did prevent Ser(536) phosphorylation of the p65 subunit of NF-kappa B, an event required for maximal transcriptional activity of NF-kappa B. Inhibition of PI3-K also prevented activation of p38 mitogen-activated protein kinase and extracellular receptor-activated kinase 1/2 in TLR2-stimulated neutrophils. These results demonstrate that the PI3-K-Akt axis occupies a central role in TLR2-induced activation of neutrophils.

Animals↗

PubMed2004

Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF-kappa B.

Although oxidative stress has been thought to play a general role in the activation of NF-kappaB, the involvement of reactive oxygen species (ROS) in facilitating nuclear translocation of NF-kappaB in neutrophils has not been described. In addition, the mechanisms by which ROS modulate the transcriptional activity of NF-kappaB in response to Toll-like receptor 4 (TLR4)-dependent signaling are not well characterized. To examine these issues, oxidant-dependent signaling events downstream of TLR4 were investigated in neutrophils stimulated with LPS. Pretreatment of neutrophils with the antioxidants N-acetylcysteine or alpha-tocopherol prevented LPS-induced nuclear translocation of NF-kappaB. Antioxidant treatment of LPS-stimulated neutrophils also inhibited the production of proinflammatory cytokines (TNF-alpha, macrophage inflammatory protein-2, and IL-1beta), as well as activation of the kinases IkappaB kinase alpha, IkappaB kinase beta, p38, Akt, and extracellular receptor-activated kinases 1 and 2. The decrease in cytoplasmic levels of IkappaBalpha produced by exposure of neutrophils to LPS was prevented by N-acetylcysteine or alpha-tocopherol. Activation of IL-1R-associated kinase-1 (IRAK-1) and IRAK-4 in response to LPS stimulation was inhibited by antioxidants. These results demonstrate that proximal events in TLR4 signaling, at or antecedent to IRAK-1 and IRAK-4 activation, are oxidant dependent and indicate that ROS can modulate NF-kappaB-dependent transcription through their involvement in early TLR4-mediated cellular responses.

Acetylcysteine↗

PubMed2004

Spinal anesthesia with bupivacaine decreases cerebral blood flow in former preterm infants.

UNLABELLED: Spinal anesthesia is commonly used in former preterm infants (FPI). In these patients, hypotension induced by spinal anesthesia may impair cerebral blood flow. We measured cerebral blood flow velocity (CBFV) by transcranial Doppler ultrasound to assess the effect of hypotension induced by spinal anesthesia on cerebral hemodynamics. Twelve FPI scheduled for inguinal hernia repair were operated under spinal anesthesia using 1 mg/kg isobaric 0.5% bupivacaine. Systolic, diastolic, and mean middle cerebral artery CBFV were measured at 5 min before and 5 min and 10 min after spinal anesthesia using a transcranial pulsed Doppler ultrasonography. Arterial blood pressure and heart rate were recorded simultaneously. Cerebral arteries resistance index (RI) was calculated as RI = (peak systolic CBFV - end-diastolic CBFV)/peak systolic CBFV. Diastolic CBFV decreased significantly from 30.0 +/- 11.1 cm/s to 20.1 +/- 8.4 cm/s at 5 min and to 20.1 +/- 7.0 cm/s at 10 min. RI increased significantly from 0.7 +/- 0.1 to 0.8 +/- 0.1 at 5 min and 10 min. Systolic, diastolic, and mean arterial blood pressures decreased significantly at the same time intervals. We suggest that in FPI, spinal anesthesia induces a decrease in cerebral blood flow related to changes in arterial blood pressure. Whether these changes have deleterious consequences remains to be determined. IMPLICATIONS: In former preterm infants having spinal anesthesia with bupivacaine, a decrease in cerebral blood flow velocity is displayed by middle cerebral artery transcranial Doppler examination.

Anesthesia, Spinal↗

PubMed2003

Modulation of bone marrow-derived neutrophil signaling by H2O2: disparate effects on kinases, NF-kappaB, and cytokine expression.

Reactive oxygen species (ROS), including hydrogen peroxide (H2O2), are generated in increased amounts in pathological, biological processes and can play a role in signal transduction. Neutrophils often accumulate in acute inflammatory reactions, at sites where elevated concentrations of ROS are present. ROS have been demonstrated to participate in the activation of intracellular signaling pathways, including those involved in modulating nuclear accumulation and transcriptional activity of NF-kappaB. However, the role of ROS in affecting such events in neutrophils has not been examined. Using exposure of murine bone marrow neutrophils to H2O2 as a model of oxidative stress, we found both strong and persistent activation of ERK1/2, p38, JNK, and PKB, but not the p21-activated kinase. Stimulating the bone marrow-derived neutrophils with H2O2 did not affect nuclear translocation of NF-kappaB. However, production and secretion of the proinflammatory cytokine TNF-alpha in LPS-stimulated neutrophils were inhibited by H2O2. Exposure of LPS- or TNF-alpha-stimulated neutrophils to H2O2 decreased nuclear translocation of NF-kappaB. LPS-induced activation of the transcriptional factor AP-1 was also inhibited by H2O2. This inhibition of nuclear accumulation of NF-kappaB by H2O2 was not caused by an impaired capacity of LPS to stimulate the IKK pathway or to direct oxidative effects on NF-kappaB but rather reflected diminished degradation of IkappaB-alpha. These results indicate that oxidative stress, despite being able to selectively activate intracellular kinases in bone marrow-derived neutrophils, also inhibits NF-kappaB activation and associated TNF-alpha expression. Such inhibitory effects on neutrophil activation may limit tissue damage produced by oxidative stress.

Animals↗

PubMed2003

Toll-like receptor-mediated tumor necrosis factor and interleukin-10 production differ during systemic inflammation.

Major trauma is associated with a decreased capacity of patients' leukocytes to produce proinflammatory cytokines on in vitro stimulation. We studied leukocytes from 48 patients with trauma and showed that this hyporeactivity was restricted to gram-negative bacteria, Escherichia coli endotoxin, and unmethylated bacterial DNA, whereas Leptospira interrogans endotoxin-induced tumor necrosis factor production was similar to that observed with healthy donors. As well, tumor necrosis factor and interleukin-6 production in response to gram-positive bacteria was not altered. The expression of toll-like receptor (TLR) 2 was not reduced on patients' monocytes as compared with healthy control subjects, whereas that of TLR4 was reduced. However, the hyporeactivity to gram-negative bacteria and E. coli endotoxin cannot be fully explained by the downregulation of TLR4. Indeed, unlike proinflammatory cytokines, after stimulation with these microbial products the release of antiinflammatory cytokines was increased as compared with healthy control subjects. The increased interleukin-10 production was analyzed in terms of intracellular signaling in peripheral blood mononuclear cells from patients with trauma: our results suggest the involvement of p38 mitogen-activated protein kinase, Sp-1 transcription factor, heterotrimeric Gi protein, and phosphatidylinositol-3'-kinase. In conclusion, the immunodysregulation described for patients with trauma is not a generalized phenomenon but depends on the stimulus and the signaling pathway.

APACHE↗

PubMed2002

Differential effects of aprotinin and tranexamic acid on endotoxin desensitization of blood cells induced by circulation through an isolated extracorporeal circuit.

OBJECTIVE: To compare the effects of aprotinin and tranexamic acid on blood cytokine secretion induced by the circulation of blood through an isolated extracorporeal circuit. DESIGN: Prospective, placebo-controlled study. SETTING: University hospital. PARTICIPANTS: Healthy volunteers (n = 18). INTERVENTIONS: Blood (400 mL) first was drawn from volunteers, then circulated through an isolated extracorporeal circuit. Three groups were compared depending on the addition or not of an antifibrinolytic agent in the circuit (control group [n = 8], tranexamic group [n = 5], aprotinin group [n = 5]). Samples for measurement were taken before and at different time points after the start of circulation through the extracorporeal circuit. Cytokine (tumor necrosis factor-alpha, interleukin [IL]-6, IL-8, and IL-10) concentrations in the plasma and in the supernatant of lipopolysaccharide-stimulated whole blood cell cultures were analyzed. MEASUREMENTS AND MAIN RESULTS: In the control and tranexamic acid groups, tumor necrosis factor-alpha, IL-6, and IL-10 secretion by whole blood cell cultures were rapidly decreased, whereas IL-8 secretion was unaffected. In the aprotinin group, IL-8 secretion was also decreased (p < 0.05). CONCLUSION: These results show that aprotinin, but not tranexamic acid, modulates the inflammatory response by reducing the IL-8 secretion of blood cells activated by contact with foreign surfaces.

Antifibrinolytic Agents↗

PubMed2002

The hemodynamic effects of pediatric caudal anesthesia assessed by esophageal Doppler.

UNLABELLED: Pediatric caudal anesthesia is an effective method with an infrequent complication rate. However, little is known about its cardiovascular consequences. Transesophageal Doppler, a noninvasive method, provides the opportunity for a reappraisal of the hemodynamic effects of this technique. After parental informed consent, we studied 10 children aged 2 mo to 5 yr who were scheduled for lower abdominal surgery. General anesthesia was induced using sevoflurane and was followed by the insertion of a transesophageal Doppler probe. Caudal anesthesia was performed using 1 mL/kg of 0.25% bupivacaine with 1/200,000 epinephrine. Hemodynamic variables were collected before and after caudal anesthesia. No complications arose during insertion of the probe. The mean time between the two sets of measurements was 15 min. Heart rate, systolic, diastolic, and mean arterial blood pressures were not modified by caudal anesthesia. Descending aortic blood flow increased significantly from 1.14 to 1.92 L/min. (P = 0.0002). Aortic ejection volume increased from 8.5 to 14.5 mL (P = 0.0002). Aortic vascular resistances decreased from 6279 to 3901 dynes. s(-1) x m(-5) (P = 0.005). Caudal anesthesia did not affect heart rate and mean arterial blood pressure but induced a significant increase in descending aortic blood flow. IMPLICATIONS: Although pediatric caudal anesthesia does not alter heart rate nor arterial blood pressure, significant changes occur in regional blood flow distribution. Descending aortic blood flow increases significantly after caudal anesthesia, whereas lower body vascular resistances decrease.

Anesthesia, Caudal↗

PubMed2002

Cortisol response to corticotropin stimulation in trauma patients: influence of hemorrhagic shock.

BACKGROUND: An abnormal adrenocortical function and a vasopressor dependency have been demonstrated during septic shock. Because trauma and hemorrhage are the leading causes of noninfectious inflammatory syndromes, the goal of this study was to assess the adrenal reserve of trauma patients and its relation with clinical course. METHODS: Cortisol response to an intravenous corticotropin bolus was obtained in 34 young trauma patients (Injury Severity Score =29.1 +/- 7.3) at the end of the resuscitative period ("early phase") and at the end of the first posttraumatic week ("late period"). Cortisol response less than +9 g/dl defined an impaired adrenal function, and the corresponding patient was called a nonresponder. According to the early response, hemorrhagic shock, circulating interleukin-6, need for vasopressor therapy, subsequent organ dysfunction and infection, and outcomes were studied. RESULTS: Sixteen patients (47%) were nonresponders at the end of the early phase. Hemorrhagic shock was more frequent (69 vs. 28%; = 0.037) and interleukin-6 concentrations were higher (728 +/- 589 vs. 311 +/- 466 pg/ml; = 0.048) in these patients. The early cortisol responses were negatively correlated with the concomitant interleukin-6 serum concentrations (r(2) = 0.298; = 0.003). Four early nonresponders (and shock patients) remained nonresponders during the late phase (25%). Morbidity and mortality were similar in early nonresponders and responders. The duration of norepinephrine treatment and the total amount of infused drug were significantly higher in early nonresponders. CONCLUSIONS: A sustained impairment of adrenal reserve is frequently observed in trauma patients. This abnormal cortisol response to corticotropin stimulation is related with the inflammatory consequences of hemorrhagic shock and is followed by a prolonged vasopressor dependency.

Adolescent↗