Biomedical subjects
Publications and source records attributed to Dan Benhamou.
A 53-year-old healthy man underwent elective laparoscopic, extraperitoneal, right-sided herniorrhaphy. Postoperatively, he complained of chest pain on inspiration. Chest x-ray and computed tomographic scan revealed a pneumomediastinum and a right-sided pneumothorax. Previous case reports and possible etiologies are reviewed.
BACKGROUND: Available literature on pregnant women with severe pulmonary hypertension (PH) relies mainly on anecdotal case reports and two series only. METHODS: The authors reviewed the charts of all pregnant women with severe PH who were followed up at their institution during the past 10 yr, to assess the multidisciplinary treatment and outcome of these patients. RESULTS: Fifteen pregnancies in 14 women with severe PH were managed during this period: There were 4 cases of idiopathic pulmonary arterial hypertension (PAH), 6 cases of congenital heart disease-associated PAH, 1 case of fenfluramine-associated PAH, 1 case of mixed connective tissue-associated PAH, 1 case of human immunodeficiency virus-associated PAH, and 2 cases of chronic thromboembolic PH. PH presented during pregnancy in 3 patients. Two patients died before delivery at 12 and 23 weeks' gestation. Four patients had vaginal deliveries with regional anesthesia: One died 3 months postpartum, one worsened, and two remained stable. Four had cesarean deliveries during general anesthesia: One died 3 weeks postpartum, one worsened, and two remained stable. Five had cesarean deliveries during low-dose combined spinal-epidural anesthesia: One died 1 week postpartum, and four remained stable. There were two fetal deaths: one related to therapeutic abortion at 21 weeks' gestation and one stillbirth at 36 weeks' gestation followed by the death of the mother 1 week later. CONCLUSIONS: Despite the most modern treatment efforts, the maternal mortality was 36%. Scheduled cesarean delivery during combined spinal-epidural anesthesia seemed to be an attractive approach, but there was no evidence of actual benefit. Therefore, pregnancy must still be discouraged in patients with severe PH.
BACKGROUND: The analgesic efficacy of ketoprofen has been shown after moderate- and severe-pain surgery, and the analgesic efficacy of nefopam has been shown after moderate-pain surgery. The aim of this study was to define the median effective analgesic doses of each drug and to determine whether the interaction of nefopam and of ketoprofen is synergistic. METHODS: Seventy-two patients scheduled to undergo moderately painful surgery were enrolled in one of three groups. The dose of nefopam and ketoprofen received by a particular patient was determined by the response of the previous patient of the same group, using an up-and-down technique. Initial doses were 18 and 40 mg, with dose adjustment intervals of 2 and 5 mg, in the nefopam and ketoprofen groups, respectively. The initial doses of nefopam and ketoprofen were 8 and 20 mg, respectively, in the nefopam-ketoprofen group, with the same dose adjustment intervals. Analgesic efficacy was defined as a decrease to less than 3 on a 0-10 numeric pain scale, 45 min after the beginning of drug infusion. RESULTS: The median effective analgesic dose (median value and 95% confidence interval) of nefopam and ketoprofen were, respectively, 28 mg (17-39 mg) and 30 mg (14-46 mg). The median effective analgesic dose of the combination was 1.75 mg (0.9-2.3 mg) for nefopam and 4.3 mg (2.2-6.5 mg) for ketoprofen. CONCLUSION: The isobolographic analysis demonstrated that the combination of the two drugs produces effective analgesia with an important synergistic interaction.
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.
Infraclavicular brachial plexus block is used less than other techniques of regional anesthesia for upper-limb surgery. We describe a modified coracoid approach to the infraclavicular brachial plexus using a double-stimulation technique and assess its efficacy. Patients undergoing orthopedic surgery of the upper limb were included in this prospective study. The landmarks used were the coracoid process and the clavicle. The needle was inserted in the direction of the top of the axillary fossa (in relation to the axillary artery), with an angle of 45 degrees. Using nerve stimulation, the musculocutaneous nerve was identified first and blocked with 10 mL of 1.5% lidocaine with 1:400,000 epinephrine. The needle was then withdrawn and redirected posteriorly and medially. The radial, ulnar, or median nerve was then blocked. The block was tested every 5 min for 30 min. The overall success rate, i.e., adequate sensory block in the 4 major nerve distributions at 30 min, was 92%, and 6% of the patients required supplementation. Five patients required general anesthesia. No major complications were observed. This modified infraclavicular brachial plexus block using a double-stimulation technique was easy to perform, had frequent success, and was safe in this cohort.
Tramadol is a centrally-acting analgesic drug. In a search of an effective balanced analgesia technique with a morphine-sparing component, we studied the median effective analgesic doses (ED(50)) of tramadol, morphine, and their combination to determine the nature of their interaction using an isobolographic analysis. In this double-blind, randomized, two-stage prospective study, 90 postoperative patients were enrolled in one of three groups. The dose of tramadol and morphine received by a particular patient was determined using an up-down allocation technique. Initial doses and increments were, respectively, 100 mg and 10 mg in the tramadol group and 5 mg and 1 mg in the morphine group. In the second part, a 40:3 tramadol:morphine dosing ratio was used. The threshold of effective analgesia was defined as 3 or less on a numerical pain score (0-10). Isobolographic analysis was subsequently applied. The ED(50) values (95% confidence interval) of tramadol and morphine were, respectively, 86 mg (57-115 mg) and 5.7 mg (4.2-7.2 mg). The ED(50) of the combination was 72 mg (62-82 mg) for tramadol and 5.4 mg (4-6.6.2 mg) for morphine. The combination of tramadol and morphine was infra-additive and thus not recommended for postoperative analgesia.
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.
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BACKGROUND: Newborns and infants seem to be at greater risk of bupivacaine cardiotoxicity than adults do. Few experiments have studied the effects of local anesthetics on myocardium associated with developmental changes, and their conclusions are conflicting. The authors compared the effects of bupivacaine on an isolated heart preparation in newborn and adult rabbits. METHODS: The authors used a constant-flow, nonrecirculating Langendorff preparation paced atrially. Adult and newborn rabbit hearts were exposed to step-increasing concentrations of bupivacaine. For each concentration, heart rate was modified with pacing from 180 to 360 beats/min by increments of 30 beats/min. QRS complex duration (index of ventricular conduction) and the first derivative of left ventricular pressure (index of contractility) were measured. The two groups were compared using an Emax model. RESULTS: In newborn and adult rabbits, QRS complex duration increased with increasing bupivacaine concentration. No difference was observed between neonatal and adult hearts. Contractility decreased with increasing bupivacaine concentration. Newborn rabbits were approximately three times more sensitive than adult rabbits to the effects of bupivacaine. However, the concentration leading to 50% decrease in the first derivative of left ventricular pressure was much higher than the concentration leading to half maximum increase in QRS complex duration. CONCLUSIONS: In conclusion, using a whole organ preparation, the authors demonstrated that bupivacaine induces similar impairment in ventricular conduction in newborn and adult rabbits. In particular, the tonic and the phasic blocks were of similar intensity in both groups. Conversely, the effect of bupivacaine on contractility was markedly higher in newborn rabbits than in adult rabbits. Also, contractility was less impaired than ventricular conduction in both groups.
BACKGROUND: The incidence and significance of troponin I release and its mechanism are unknown in severe trauma patients. The characteristics of this release were prospectively studied in such patients and correlated with presence of shock, existence of myocardial contusion, and outcome. METHODS: During a 24-month period, serial electrocardiogram recordings and troponin I measurements were performed in all trauma patients admitted at a surgical intensive care unit. The diagnosis of a significant myocardial contusion was made on electrocardiographic criteria. According to the time course of troponin I, three groups of patients were defined a priori: very transient (</= 12 h) and limited release (troponin I < 2 microg/l), transient (</= 36 h) and significant release (troponin I >/= 2 microg/l), and sustained (> 36 h) and significant release (troponin I > 2 microg/l). In the last group, coronary artery angiography was performed. RESULTS: The incidence of troponin I release was 12% (95% confidence interval [CI], 9.6-14.4%) in 728 patients. A significant myocardial contusion was found in 35 patients (5%; 95% CI, 3.4-6.6%) and may occur in the absence of chest trauma and without troponin I release. Sensitivity, specificity, and positive and negative predictive values of troponin I for the diagnosis of myocardial contusion were 63, 98, 40, and 98%, respectively. Troponin I release was observed in 54 early (> 48 h) survivors (7%; 95% CI, 5.6-9.6%) without preexisting coronary artery disease. A sustained and significant release of troponin I (17 patients) was frequently associated with chest trauma (82%) and constantly with electrocardiographic abnormalities. A coronary artery injury was found in 7 patients (2 major and 5 minor vascular injuries) (1% of the whole group; 95% CI, 0.4-2.0%). Mortality was similar in early survivors with (15%; 95% CI, 7-27%) or without (12%; 95% CI, 9-14%) troponin I release. The odds ratio for late mortality was 1.32 (95% CI, 0.61-2.85) in patients with troponin I release. CONCLUSIONS: Serial electrocardiogram recordings and troponin I assessments may be proposed for initial screening in high-risk trauma patients to detect anatomical cardiac injuries through the time course of circulating protein. Troponin I release does not have a prognosis value in trauma patients.
We studied the consequences of an early phase of TNFalpha-induced LV dysfunction and of its treatment by isoproterenol on an isolated rabbit heart preparation. Two dosages of TNFalpha (2 and 4 microg) were infused, followed by isoproterenol (ISO), infused by increasing concentrations from 10 to 10 M. Left ventricular developed pressure (DP) was recorded. Creatine kinase (CKtot) and cardiac Troponin I (cTnI) were measured in the effluent perfusate. An anatomic score was calculated by histologic examination of the hearts while a structural analysis of cTnI was done. TNFalpha induced a dose-dependent decrease in DP (-43 +/- 18% for 4 microg) without change in coronary vascular resistances, which was not followed by biochemical or structural abnormalities. TNFalpha reduced the maximum effect (Emax) of ISO on DP (mean DeltaDPmaxISO = -40% for 4 microg) without change in the concentration leading to half Emax (ED50ISO). ISO treatment of TNFalpha (4 microg)-induced LV dysfunction resulted in a selective release of cTnI, myocardial tissue contraction bands, and a significant proteolysis of cTnI. Within the limits of the model, the myocardial injury reported during severe sepsis would not be related to an early cytotoxic effect of TNFalpha but could be attributed to an enhancement of the effects of isoproterenol by TNFalpha.
BACKGROUND: Left ventricular ejection time (LVET) measured in central arteries is modified during hypovolemia. We compared modifications of the pulse wave in a central artery (carotid) and in a peripheral artery (digital) during central hypovolemia induced by lower body negative pressure (LBNP) in conscious volunteers. METHODS: Hypovolemia was simulated with progressive LBNP (baseline, -10, -20, and -30 mm Hg) in nine young healthy volunteers. The carotid arterial pressure waveform was recorded using a Millar tonometric method. The digital pulse wave was measured with a volume-clamp method (Finapres) and the stroke volume with a thoracic impedance method (Biomed). RESULTS: Mean arterial pressure did not change during LBNP. Compared with baseline values, heart rate increased significantly at the -30 mm Hg level (68 +/- 13 beats/min vs. 59 +/- 11 beats/min), and stroke volume decreased as soon as -10 mm Hg was achieved (113 +/- 41 mL vs. 127 +/- 35 mL). Both carotid and digital LVET decreased significantly at the -10 mm Hg level (337 +/- 26 and 339 +/- 24 ms vs. 360 +/- 35 and 361 +/- 24 ms, respectively). CONCLUSION: Peripheral LVET could reflect variation of central LVET during LBNP and be a reliable noninvasive parameter for monitoring hypovolemia.
UNLABELLED: The aim of this study was to characterize the nature of analgesic interaction between nefopam and morphine administered i.v. for postoperative pain after minor surgery. To do so, we defined the median effective analgesic dose (ED(50)) for each drug and also the median ED(50) of their combination and compared them using the isobolographic method. Determination of median effective doses was performed by the up-and-down sequential drug administration in a two-stage study. First, in a prospective, randomized, double-blinded study, we enrolled 60 patients with mild to moderate pain after minor surgery; this was followed by an open study enrolling 30 patients. The end-point was a pain score less than 3 on a Numerical Pain Scale (0-10). Initial doses were 16 mg in group N, 5 mg in group M, and 7.5 mg of N combined with 2.5 mg of M in group N+M. The testing interval was 2 mg in group N, 1 mg in group M, and 1.5 mg of N combined with 0.5 mg of M in group N+M. ED(50) (95% confidence interval) was 5 mg (4-6 mg) for morphine, 18 mg (16-18 mg) for nefopam, and 4 mg (3.5-4.5 mg) with 12 mg (10.5-13.5 mg) for the combination of morphine and nefopam administered at a 3:1 dose ratio. Isobolographic analysis demonstrated a significant infra-additive interaction. The incidence of side effects did not differ significantly among morphine, nefopam, and their combination. These findings suggest that the combination of nefopam and morphine does not offer any advantage compared to each drug administered i.v. or alone after minor surgery. This study is the first to define the ED(50) of nefopam and morphine in postoperative patients. In conclusion, the addition of nefopam has a morphine-sparing effect, but the combination is infra-additive. IMPLICATIONS: Pharmacologic interaction between nefopam and morphine shows infra-additivity but their combination may be clinically useful as morphine consumption is decreased in postoperative patients.
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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.
A National Confidential Inquiry was conducted among death certificators and anaesthetists. A sample of 3700 death certificates from the year 1999 were randomised, after selection of words relating to anaesthesia, surgery, obstetrics, endoscopy, procedural complications, and violent death, with different ratios according to the words and the age; 500 additional certificates relating to deaths in hospital were evaluated to verify the exhaustive nature of the mention of procedures in the certificates. The certificator was sent a simplified form each time the role of the procedure in death could not be excluded (response rate 97%). The anaesthetist was offered a peer review whenever the role of the anaesthetic procedure could not be ruled out (uptake rate 97%). An expert committee analysed the (anonymized) files to determinate the mechanism of the accident and its relationship to anaesthesia. The mortality rates were estimated from the 1996 "Anaesthesia in France" survey. The annual rates of deaths that were totally or partially related to anaesthesia were respectively 7 (CI95%: 2-12) and 47 (31-63) per million. These mortality rates increased with comorbidity, from 4 per million in patients of ASA physical status class 1 to 554 per million in class 4. Similarly, these rates increased with age, from 7 per million in patients less than 45 years old, to 32 in older patients. Most accidents were of ventilatory (38%: airway management: 6%, aspiration pneumonitis: 9%), cardiac (31%: ischaemia: 25%, including anaemia-related), and vascular origin (30%: hemorrhage: 12%, vasodilation by spinal anaesthesia: 6%, anaphylaxis: 3%). The main surgical procedures involved were orthopaedic (50%: hip fracture, haemorrhagic surgery) and digestive (24%: occlusion, peritonitis). INSERM had previously collected data on complications associated with anaesthesia between 1978 and 1982: the annual rates of deaths that were totally or partially related to anaesthesia were respectively 76 and 263 per million. Compared to these previous data, the anaesthesia-related mortality rate fell ten-fold over the last two decades, while the number of anaesthetic procedures at least doubled. In addition, the number of procedures involving old people and patients with poor physical status was multiplied by four. It seems logical to attribute these results to safety and practice guidelines published after the previous inquiry. Progress remains to be made: the present rate of 1/145000 will serve as a basis for systematic analysis of accidents.
BACKGROUND: This study was designed to determine and compare the minimum local analgesic concentrations of levobupivacaine and ropivacaine when used in epidural obstetric analgesia. METHODS: In a double-blind study, healthy women requiring epidural analgesia for labor pain were randomized to receive either ropivacaine or levobupivacaine. Drugs were administered as a 20-ml epidural bolus. The concentration of each started at 0.11% and increased or decreased at intervals of 0.01%, depending on the response of the previous patient, using the technique of up-down sequential allocation. Minimum local analgesic concentrations were calculated using the formula of Dixon and Massey. Efficacy was assessed using visual analog pain scores and motor and sensory block assessments, and safety was assessed by recording maternal and fetal/neonate vital signs and adverse events. RESULTS: Forty-seven patients received levobupivacaine, and 47 received ropivacaine. Minimum local analgesic concentrations for levobupivacaine (0.077%; 95% CI, 0.058-0.096%) were lower than those for ropivacaine (0.092%; 95% CI, 0.082-0.102%). The 0.015% difference was not statistically significant. There was no notable difference between treatment groups in the proportion of patients reporting drug-related adverse events. CONCLUSIONS: Levobupivacaine was 19% more potent than ropivacaine and provided similar safety results.