Kamran Samii

Serious complications related to regional anesthesia: results of a prospective survey in France.

Background Serious complications related to regional anesthesia have previously been described primarily in case reports and retrospective surveys. The authors prospectively evaluated a multicenter series of regional anesthetics, using preplanned criteria to measure the incidence and characteristics of associated serious complications. Methods Requests were sent to 4,927 French anesthesiologists in advance of a subsequent 5-month study period. Participating anesthesiologists were asked for detailed reports of serious complications occurring during or after regional anesthetics performed by them during the study interval. Details regarding each complication then were obtained via a second questionnaire. Results The number of responding anesthesiolgists was 736. The number of regional anesthetics performed was 103,730, corresponding to 40,640 spinal anesthetics, 30,413 epidural anesthetics, 21,278 peripheral nerve blocks, and 11,229 intravenous regional anesthetics. Reports of 98 severe complications were received, with follow-up information being obtained for 97. In 89 cases, complications were attributed fully or partially to regional anesthesia. Thirty-two cardiac arrests, seven of which were fatal, occurred during the study. Of these, 26 occurred during spinal anesthesia, with 6 being fatal, 3 occurred during epidural anesthesia, and 3 more occurred during peripheral blocks. The higher incidence of cardiac arrest during spinal anesthesia (6.4 +/- 1.2 per 10,000 patients) compared with all other regional anesthesia (1.0 +/- 0.4 per 10,000 patients) was statistically significant (P < 0.05). Of 34 neurologic complications (radiculopathy, cauda equina syndrome, paraplegia), 21 were associated either with paresthesia during puncture (n = 19) or with pain during injection (n = 2), suggesting nerve trauma or intraneural injection. Twelve patients who had neurologic complications after spinal anesthetics had no paresthesia during needle placement and no pain on injection. Of these 12 patients (7 with radiculopathy and 5 with cauda equina syndrome), 9 received intrathecal hyperbaric lidocaine, 5%. The incidence of neurologic injury was significantly greater after spinal anesthesia (6 +/- 1 per 10,000 cases; P < 0.05) than after each of the other types of regional procedures (1.6 +/- 0.5 per 10,000 cases for the weighted average). Seizures attributed to elevated serum levels of local anesthetics occurred in 23 patients, but none suffered a cardiac arrest. Conclusions (1) The incidence of cardiac arrest and neurologic injury related to regional anesthesia were very low, but both were more than three SDs greater after spinal anesthesia than after other regional procedures. (2) Two thirds of the patients with neurologic deficits had either a paresthesia during needle placement or pain on injection. (3) Seventy-five percent of the neurologic deficits after nontraumatic spinal anesthesia occurred in patients who had received hyperbaric lidocaine, 5%.

Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline Service.

Background Several previous surveys have estimated the rate of major complications that occur after regional anesthesia. However, because of the increase in the use of regional anesthesia in recent years and because of the introduction of new techniques, reappraisal of the incidence and the characteristics of major complications is useful. Methods All French anesthesiologists were invited to participate in this 10-month prospective survey based on (1) voluntary reporting of major complications related to regional anesthesia occurring during the study period using a telephone hotline service available 24 h a day and managed by three experts, and (2) voluntary reporting of the number and type of regional anesthesia procedures performed using pocket booklets. The service was free of charge for participants. Results The participants (n = 487) reported 56 major complications in 158,083 regional anesthesia procedures performed (3.5/10,000). Four deaths were reported. Cardiac arrest occurred after spinal anesthesia (n = 10; 2.7/10,000) and posterior lumbar plexus block (n = 1; 80/10,000). Systemic local anesthetic toxicity consisted of seizures only, without cardiac toxicity. Lidocaine spinal anesthesia was associated with more neurologic complications than bupivacaine spinal anesthesia (14.4/10,000 vs. 2.2/10,000). Most neurologic complications were transient. Among 12 that occurred after peripheral nerve blocks, 9 occurred in patients in whom a nerve stimulator had been used. Conclusion This prospective survey based on a free hotline permanent telephone service allowed us to estimate the incidence of major complications related to regional anesthesia and to provide a detailed analysis of these complications.

Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients

OBJECTIVES To compare the efficacy of a newly available antiseptic solution (composed of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzyl alcohol), with 10% povidone iodine, on the prevention of central venous or arterial catheter colonization and infection. DESIGN Prospective, randomized clinical trial. SETTING Surgical-trauma intensive care unit (ICU) in a university hospital. PATIENTS All patients admitted to the ICU and requiring the insertion of a central venous and/or an arterial catheter from July 1, 1992 to October 31, 1993. INTERVENTIONS Patients were randomly assigned to one of two groups according to the antiseptic solution used for insertion and catheter care. The same solution was used for skin disinfection from the time of catheter insertion to the time of removal of each catheter. MEASUREMENTS AND MAIN RESULTS Catheter distal tips were quantitatively cultured when catheters were no longer necessary, if there was a suspicion of catheter-related infection, and routinely after 7 days of use for arterial catheters, or after 15 days of use for central venous catheters. The rate of significant catheter colonization (i.e., > or = 10(3) colony-forming units [cfu]/mL by quantitative culture), and catheter-related sepsis (as defined by sepsis abating following catheter removal per 1,000 catheter-days), were significantly lower in the chlorhexidine group (12 vs. 31 [relative risk 0.4, 95% confidence interval 0.1 to 0.9, p < .01] and 6 vs. 16 [relative risk 0.4, 95% confidence interval 0.1 to 1, p = 0.5], respectively). The rate of central venous catheter colonization and central venous catheter-related sepsis per 1,000 catheter-days were also significantly lower in the chlorhexidine group (8 vs. 31 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .03] and 5 vs. 19 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .02], respectively). Finally, the rate of arterial catheter colonization per 1,000 catheter-days was significantly lower in the chlorhexidine group (15 vs. 32 [relative risk 0.5, 95% confidence interval 0.1 to 1, p = .05]), whereas the rate of arterial catheter-related sepsis per 1,000 catheter-days was similar for the two study groups (8 in the chlorhexidine group vs. 10 in the povidone iodine group [relative risk 0.8, 95% confidence interval 0.1 to 2.2, p = .6]). The 0.25% chlorhexidine solution was superior to the 10% povidone iodine solution in preventing catheter colonizations and catheter-related sepsis due to Gram-positive bacteria (5 vs. 20 [p < .001], and 2 vs. 10 [p < .001], respectively), whereas the activity of the 0.25% chlorhexidine solution was nonsignificantly superior in preventing Gram-negative infections (7 vs. 4 [p = .5], and 4 vs. 2 [p = .8], respectively). CONCLUSIONS The 4% alcohol-based solution of 0.25% chlorhexidine gluconate and 0.025% benzalkonium chloride was more effective than 10% povidone iodine for insertion site care of short-term central venous and arterial catheters. This effect appeared related to a more efficacious prevention of infections with Gram-positive bacteria.

Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock

OBJECTIVES To compare in the same patient with septic shock, respective effects of epinephrine, norepinephrine, and the combination of norepinephrine and dobutamine (5 microg/kg/min) on systemic hemodynamic parameters and gastric mucosal perfusion using gastric tonometry and laser-Doppler flowmetry techniques. DESIGN Prospective, controlled, randomized, crossover study. SETTING University hospital intensive care unit. PATIENTS Twelve patients with septic shock. INTERVENTIONS Each patient received in a random succession epinephrine, norepinephrine, and norepinephrine plus dobutamine. Dosages of epinephrine and norepinephrine were adjusted to achieve a mean arterial pressure between 70 and 80 mm Hg. A laser-Doppler probe and a tonometer were introduced into the gastric lumen. MEASUREMENTS AND MAIN RESULTS The increase in gastric mucosal perfusion detected by laser-Doppler flowmetry was higher with epinephrine and the combination of norepinephrine and dobutamine than with norepinephrine alone (p < .05). In addition, the ratio of gastric mucosal perfusion (local oxygen delivery) to systemic oxygen delivery was increased after norepinephrine plus dobutamine as compared with norepinephrine alone and epinephrine (p< .05). Although values of intramucosal pH and gastroarterial PCO2 tended to be higher with norepinephrine plus dobutamine compared with those obtained with norepinephrine and epinephrine, differences were not statistically significant. CONCLUSIONS For the same mean arterial pressure in patients with septic shock, our study showed that administration of epinephrine increased gastric mucosal perfusion more than norepinephrine administration alone. Addition of dobutamine (5 microg/kg/ min) to norepinephrine improved gastric mucosal perfusion. This result could be explained by a vasodilating effect of dobutamine on gastric mucosal microcirculation.

Myocardial uptake of bupivacaine: II. Pharmacokinetics and pharmacodynamics of bupivacaine enantiomers in the isolated perfused rabbit heart.

The enantiomers of a racemic drug generally differ in their pharmacokinetic and/or pharmacodynamic properties. Because bupivacaine is a mixture of two optical isomers known to exert different toxic properties on isolated nerve preparations, we decided to use an isolated rabbit heart model with constant coronary inflow to compare the myocardial uptake kinetics of the R(+)-, S(-)-enantiomers and the racemic mixture of bupivacaine. The increase in QRS duration was also measured, and the inflow concentration-effect relationship was analyzed for the three drugs. The racemic and the two enantiomers of bupivacaine exhibited similar myocardial pharmacokinetics with a two-compartment profile for all hearts except one. All drugs showed a rapid decrease in the outflow concentration when drug administration was discontinued. The tissue/perfusate concentration ratio at steady state was similar for the three drugs. QRS widening, as well as the occurrence of severe arrhythmias, was much less pronounced in the hearts receiving the S(-) isomer than in the hearts receiving the R(+) isomer or the racemic mixture. Despite the occurrence of arrhythmias, QRS widening was adequately modelled with an Emax model. C50, the inflow perfusate concentration producing half Emax (maximal theoretical increase in QRS duration) was the same for all three drugs. The authors conclude that the S(-)-bupivacaine exerts less detrimental effects on the isolated heart of the rabbit perfused at a constant coronary flow with protein-free buffer.

Pharmacokinetics of bupivacaine following caudal anesthesia in infants.

Pharmacokinetics and protein binding of bupivacaine were studied after caudal injection of 2.5 mg/kg in 13 ASA PS 1 infants (1–6 months of age) scheduled for elective hernia repair. Blood was sampled at frequent intervals from 5 min to 600 min in all but one patients. Additional samples were taken at 720 and 840 min in five patients. Bupivacaine concentration was measured using gas chromatography. Protein binding was measured using ultrafiltration. Peak serum concentrations ranged between 0.55 and 1.93 μg/ml. The time to reach the peak ranged from 10 to 60 min. Terminal half-life (T 1/2β) was 7.7 ± 2.4 h (mean ± SD), the volume of distribution (Vss) was 3.9 ± 2.01·kg, and the total body clearance (CL) was 7.1 ± 3.2 ml·min·kg−1. The free fraction was markedly increased (0.16 ± 0.07) when compared with published adult values, and showed a highly significant negative correlation with age. Alpha 1 acid glycoprotein measured in the same infants correlated significantly with age. In conclusion, pharmacokinetics of caudal bupivacaine in infants are characterized by Cmax of total drug similar to those observed in adults after epidural injection. The free fraction is increased at least until 6 months of life. This suggests caution in the use of bupivacaine in infants until we understand the clinical significance of this increased free fraction.

Heterogeneous regional vascular responses to simulated transient hypovolemia in man

ObjectiveTo describe the evolution of systemic and regional blood flows during and after hypovolemia in humans.DesignSimulation of hypovolemia by a prolonged application of lower body negative pressure (LBNP).SettingLaboratory of Clinical Research, Surgical Intensive Care Unit of an University Hospital.Participants8 healthy male volunteers.Interventions3 successive and increasing 15min-levels of LBNP were followed by a progressive return (10 min) to atmospheric pressure, then a 60min-recovery period.Measurements and main resultsSimulated hypovolemia induced a parallel one-third decrease in cardiac output (bioimpedance), musculocutaneous (venous plethysmography) and splanchnic (ICG clearance) blood flows. Adrenergic-mediated peripheral vasoconstriction prevented any change in mean arterial pressure. The decrease in renal blood flow (PAH clearance) was limited, glomerular filtration rate (inulin clearance) unchanged and thus filtration fraction increased. All the cardiovascular and biological variables returned to pre-LBNP values during the recovery period except for splanchnic blood flow which remained below control values 60 min after the return to atmospheric pressure.ConclusionsSince a sustained splanchnic vasoconstriction follows a transient normotensive hypovolemia in healthy men despite adequate treatment considering arterial pressure and cardiac output, the therapeutic goals of fluid resuscitation after hypovolemic shock might be revisited and a supranormal value of cardiac output proposed.

Influence of Venous Return on Baroreflex Control of Heart Rate during Lumbar Epidural Anesthesia in Humans

The role of variation of venous return on baroreflex control of heart rate during lumbar epidural anesthesia was investigated in 12 unpremedicated patients. Group 1 patients (n = 6) received 8 ml of 0.5% plain bupivacaine in the epidural space (L3–4) (mean upper level of analgesia at T10). Group 2 patients (n = 6) received 8 ml of saline at the same level in the epidural space. Following the epidural injection, phenylephrine (PHE) and nitroglycerin (NTG) were employed to alter the stimulation of baroreceptor sites before and during application of lower body positive pressure (LBPP). Plasma bupivacaine, catecholamines, renin activity, and vasopressin were assayed. In contrast to saline, epidural bupivacaine induced a decrease in systolic arterial and right atrial pressures (−11 ‡ 4 and −3.2 ‡ 0.7 mmHg, respectively, mean ‡ SEM) without change in heart rate, an increase in baroreflex slopes during PHE and NTG injections (+5.9 ‡ 1.6 ms/mmHg and +2.8 ‡ 0.9 ms/mmHg, respectively), and a decrease in plasma norepinephrine (−248 ‡ 89 pg/ml). The application of LBPP restored hemodynamic and reflex variables to preepidural analgesia values, whereas plasma catecholamines decreased further. Plasma renin activity and vasopressin were not modified at any time in either groups. This study indicates that lumbar epidural anesthesia enhances cardiac vagal tone mainly through a decrease in venous return.

Role of systemic inflammatory response syndrome and infection in the occurrence of early multiple organ dysfunction syndrome following severe trauma.

ObjectiveTo evaluate the role of infection and systemic inflammatory response syndrome (SIRS) on the occurrence of early posttraumatic MODS.DesignRetrospective study.SettingUniversity Teaching Hospital ICU.Patients163 consecutive patients hospitalized for more than 48 hours following severe trauma.Measurements and main resultsThe patients were classified into two groups in respect to the existence of MODS at day 2. There was 27 patients in the MODS group and 136 patients in the no MODS group. The two groups were similar with respect to age, sex ratio and Simplified Acute Physiology Score. The MODS group had a higher mortality (52 versus 7%), Injury Severity Score (45±14 versus 31±13), hypovolemic shock rate (74 versus 30%), massive volume replacement rate (59 versus 6%) and SIRS rate (81 versus 54%) than the no MODS group (p<0.05). The rate of infection was similarly low in the MODS and no MODS group (4 versus 6% respectively).ConclusionEarly MODS is often associated with hypotension and massive volume administration but very rarely with infection, despite the high rate of SIRS.

Morphine in postoperative patients: pharmacokinetics and pharmacodynamics of metabolites.

BACKGROUND: There is great variability in the need for morphine in the postoperative period. We performed a pharmacokinetic–pharmacodynamic study considering the potential effect of the two main metabolites of morphine. METHODS: Fifty patients with moderate to severe pain received morphine as an IV titration, followed by IM administration postoperatively. The plasma concentration of morphine, morphine-6-glucuronide (M-6-G), morphine-3-glucuronide (M-3-G), and pain intensity were measured at frequent intervals. Pharmacokinetic and pharmacodynamic fitting was performed with the software NONMEM. RESULTS: The pharmacokinetics were largely predictable. M-6-G and M-3-G clearances were markedly decreased in patients with renal failure. The pharmacodynamics was less predictable, with an important interindividual variability. M-6-G was 7.8 times more potent than morphine, but the average time to peak concentration in the effect compartment after a bolus injection of morphine was 4.25 h for M-6-G, when compared to 0.33 h for morphine. M-3-G showed mild inhibition of the analgesic properties of morphine and of M-6-G. The time to M-3-G peak concentration in the effect compartment after a bolus injection of morphine was 10 h. CONCLUSIONS: M-6-G is a potent opioid agonist and M-3-G a mild opioid antagonist. Both are poorly excreted in patients with renal failure. However, the metabolism of morphine was rapid when compared to the transfer of metabolites through the blood–brain barrier, which appears to be the limiting process. Because poor analgesia due to M-3-G’s effect may occur in some patients after 1 or 2 days, a switch to other molecules should be considered.