Laurent Beydon

Clonidine Comparably Decreases the Thermoregulatory Thresholds for Vasoconstriction and Shivering in Humans

Background:Clonidine stops postoperative shivering, but its underlying mechanism of action is unknown. Clonidine may impair central control of thermoregulation or act on peripheral receptors. Accordingly, the authors tested the hypothesis that clonidine reduces both the vasoconstriction and shivering thresholds, a pattern consistent with central thermoregulatory impairment. Methods:Seven healthy volunteers participated in the study. Thermoregulatory vasoconstriction was evaluated using forearm minus fingertip, skin-temperature gradients; values exceeding 4° C were considered to be significant vasoconstriction. Systemic oxygen consumption (&OV0312;O2) was measured with a canopy system. In addition, shivering was qualitatively evaluated using a simple scale, graduated from 0 (no shivering) to 2 (intense shivering). The tympanic membrane temperatures triggering significant vasoconstriction and grade 1 shivering were considered to be the thresholds for the two thermoregulatory responses. Measurements were performed after a 10-min steady state period and during cooling by central venous infusion of Ringers lactate solution at 4° C. Each subject was evaluated at two sessions, separated by at least 48 h. They were randomly and blindly assigned to received either an intravenous bolus of 75 µg clonidine or a placebo before cooling. When the shivering score equaled 2, 75 µg clonidine was injected intravenously, and repeated if necessary, to completely stop shivering. Results:Clonidine significantly decreased the thermoregulatory threshold for shivering by 0.6 ± 0.3° C (mean ± SD). Similarly, the threshold for cutaneous vasoconstriction was significantly reduced by 0.5 ± 0.2° C. Additional clonidine administration always stopped shivering, at whatever temperature it occurred. Conclusions:This study confirms that clonidine administration stops shivering, and suggests that it acts by impairing central thermoregulatory control. That an additional dose of clonidine stops shivering in subjects already given one dose, indicates that the effect of clonidine is dose dependent.

Closed-loop Coadministration of Propofol and Remifentanil Guided by Bispectral Index: A Randomized Multicenter Study

BACKGROUND:We have developed a proportional-integral-derivative controller allowing the closed-loop coadministration of propofol and remifentanil, guided by a Bispectral Index (BIS) monitor, during induction and maintenance of general anesthesia. The controller was compared with manual target-controlled infusion. METHODS:In a multicenter study, 196 surgical patients were randomly assigned to dual closed-loop or manual administration of propofol and remifentanil. Comparison between groups was evaluated by calculating a global score that characterized the overall performance of the controller including the percentage of adequate anesthesia, defined as BIS between 40 and 60, the median absolute performance error, and wobble. Secondary outcomes included occurrence of burst suppression ratio, time to tracheal extubation, and drug consumption. RESULTS:Eighty-three patients assigned to dual-loop control and 84 patients assigned to manual control completed the study. The global score and the percentage of time with BIS between 40 and 60 were better in the dual-loop group (26 ± 11 vs 43 ± 40, P < 0.0001; 82% ± 12% vs 71% ± 19%, P < 0.0001). Overshoot (BIS <40), undershoot (BIS >60), and burst suppression ratio were all significantly less common in the dual-loop group. Modifications to the propofol and remifentanil infusions were more frequent, and adjustments smaller in the dual-loop group. Remifentanil consumption was greater (0.22 ± 0.07 vs 0.16 ± 0.07 &mgr;g · kg−1 · min−1; P < 0.0001) and the speed to tracheal extubation was shorter (10 ± 4 vs 11 ± 5 minutes; P = 0.02) in the dual-loop group. CONCLUSION:The controller allows the automated delivery of propofol and remifentanil and maintains BIS values in predetermined boundaries during general anesthesia better than manual administration.

Correlation between Cerebral Oxygen Saturation Measured by Near-infrared Spectroscopy and Jugular Oxygen Saturation in Patients with Severe Closed Head Injury

UNLABELLED Near-infrared spectroscopy has been used to monitor cerebral oxygen saturation during cerebral circulatory arrest and carotid clamping. However, its utility has not been demonstrated in more complex situations, such as in patients with head injuries. The authors tested this method during conditions that may alter the arteriovenous partition of cerebral blood in different ways. METHODS The authors compared changes in measured cerebral oxygen saturation and other hemodynamic parameters, including jugular venous oxygen saturation, in nine patients with severe closed head injury during manipulation of arterial carbon dioxide partial pressure and after mean arterial pressure was altered by vasopressors. RESULTS The Bland and Altman representation of cerebral oxygen saturation versus jugular oxygen saturation showed a uniform scatter. Values for changing arterial carbon dioxide partial pressure were: bias = 1.1%, 2 SD = +/-21%, absolute value; and those for alterations in mean arterial pressure: bias = 3.7%, 2 SD = +/-24%, absolute value. However, a Bland and Altman plot of changes in cerebral oxygen saturation versus changes in jugular oxygen saturation had a negative slope (alteration in arterial carbon dioxide partial pressure: bias = 2.4%, 2 SD = +/-17%, absolute value; alteration in mean arterial pressure: bias = -4.9%, 2 SD = +/-31%, absolute value). Regression analysis showed that changes in cerebral oxygen saturation were positively correlated with changes in jugular venous oxygen saturation during the carbon dioxide challenge, whereas correlation was negative during the arterial pressure challenge. CONCLUSIONS Cerebral oxygen saturation assessed by near-infrared spectroscopy does not adequately reflect changes in jugular venous oxygen saturation in patients with severe head injury. Changes in arteriovenous partitioning, infrared-spectroscopy contamination by extracerebral signal, algorithm errors, and dissimilar tissue sampling may explain these findings.

AnaConDa reflection filter: bench and patient evaluation of safety and volatile anesthetic conservation.

BACKGROUND:The AnaConDa® filter permits administration of volatile anesthetic without the use of an anesthesia machine. It is intended for use in the intensive care unit. METHODS:We studied the AnaConDa® reflection filter on the bench and in anesthetized patients. The bench analysis used a test lung, a gas analyzer, an intensive care ventilator, the AnaConDa® filter, and a syringe pump. We studied a range of tidal volume, respiratory rate, and positive end-expiratory pressure values. We simulated errors during syringe refilling and patient transportation. In 15 anesthetized patients, we used the AnaConDa® with constant ventilation variables, a constant sevoflurane infusion rate (4–5 mL/h), and two consecutive fresh gas flow levels. RESULTS:In the bench study, the expired volatile anesthetic fraction decreased linearly with respiratory frequency at constant minute ventilation, and decreased markedly in a hyperbolical manner when tidal volume increased at a constant respiratory rate. Changing the positive end-expiratory pressure level and inspiration/expiration ratio did not modify the AnaConDa®’s performance. Several safety failures were observed: refilling caused a transient change in AnaConDa® output because of a pumping effect, and a standard Luer lock made it possible to connect the halogenate syringe on an IV infusion line. In anesthetized patients, reducing fresh gas flow from 8 to 1 L/min led to a median 40% increase in the expired volatile anesthetic fraction. CONCLUSIONS:This study shows that the device is generally reliable, but that there are several conditions under which it might deliver more anesthetic than intended.

Comparison of infection rate with the use of antibiotic-impregnated vs standard extraventricular drainage devices: a prospective, randomized controlled trial.

BACKGROUND External ventricular drainage (EVD) catheters provide reliable and accurate means of monitoring intracranial pressure and alleviating elevated pressures via drainage of cerebrospinal fluid (CSF). CSF infections occur in approximately 9% of patients. Antibiotic-impregnated (AI) EVD catheters were developed with the goal of reducing the occurrence of EVD catheter-related CSF infections and their associated complications. OBJECTIVE To present an international, prospective, randomized, open-label trial to evaluate infection incidence of AI vs standard EVD catheters. METHODS Infection was defined as (1) proven infection, positive CSF culture and positive Gram stain or (2) suspected infection: (A) positive CSF culture with no organisms identified on initial Gram stain; (B) negative CSF culture with a gram-positive or -negative stain; (C) CSF leukocytosis with a white blood cell/red blood cell count >0.02. RESULTS Four hundred thirty-four patients underwent implantation of an EVD catheter. One hundred seventy-six patients in the AI-EVD cohort and 181 in the standard EVD catheter cohort were eligible for evaluation of infection. The 2 groups were similar in all clinical characteristics. Proven infection was documented in 9 (2.5%) patients (AI: 4 [2.3%] vs standard: 5 [2.8%], P = 1.0). Suspected infection was documented in 31 (17.6%) patients receiving AI and 37 (20.4%) patients receiving standard EVD catheters, P = .504. Duration of time to suspected infection was prolonged in the AI cohort (8.8 ± 6.1 days) compared with the standard EVD cohort (4.6 ± 4.2 days), P = .002. CONCLUSION AI-EVD catheters were associated with an extremely low rate of catheter-related infections. AI catheters were not associated with risk reduction in EVD infection compared to standard catheters. Use of AI-EVD catheters is a safe option for a wide variety of patients requiring CSF drainage and monitoring, but the efficacy of AI-EVD catheters was not supported in this trial.

Changes in intracranial pressure and cerebral autoregulation in patients with severe traumatic brain injury

Background Impaired cerebral autoregulation is frequent after severe traumatic head injury. This could result in intracranial pressure fluctuating passively with the mean arterial pressure. Objective This study examines the influence of autoregulation on the amplitude and direction of changes in intracranial pressure in patients with severe head injuries during the management of cerebral perfusion pressure. Design Prospective study. Setting Neurosurgical intensive care unit Patients A total of 42 patients with severe head injuries. Interventions Continuous recording of cerebral blood flow velocity, intracranial pressure, and mean arterial pressure during the start or change of continuous norepinephrine infusion. Measurements and Main Results Cerebrovascular resistance was calculated from the cerebral perfusion pressure and middle cerebral artery blood flow velocity. The strength of autoregulation index was calculated as the ratio of the percentage of change in cerebrovascular resistance by the percentage of change in cerebral perfusion pressure before and after 121 changes in mean arterial pressure at constant ventilation between day 1 and day 18 after trauma. The strength of autoregulation index varied widely, indicating either preserved or severely perturbed autoregulation during hypotensive or hypertensive challenge in patients with or without intracranial hypertension at the basal state (strength of autoregulation index, 0.51 ± 0.32 to 0.71 ± 0.25). The change in intracranial pressure varied linearly with the strength of autoregulation index. There was a clinically significant change in intracranial pressure (≥5 mm Hg) in the same direction as the change in mean arterial pressure in five tracings of three patients. This was caused by the mean arterial pressure dropping below the identified lower limit of autoregulation in three tracings for two patients. It seemed to be caused by a loss of cerebral autoregulation in the remaining two tracings for one patient. Conclusion Cerebral perfusion pressure–oriented therapy can be a safe way to reduce intracranial pressure, whatever the status of autoregulation, in almost all patients with severe head injuries.

Changes in cerebral hemodynamics after a single dose of clonidine in severely head-injured patients

alpha2-Adrenergic agonists induce cerebral vasoconstriction, reduce intracranial pressure (ICP) in experimental animals and may be useful in the hemodynamic management of head-injured patients. We studied the effects of the alpha2 agonist clonidine on the cerebral circulation in 12 head-injured patients (Glasgow Coma Scale score < 8). Middle cerebral artery flow velocity (MCAV), ICP, mean arterial pressure (MAP), and cerebral perfusion pressure (CPP), were continuously recorded before (T0), at the end (T1), and 30 min after (T2) a 10-min intravenous (IV) infusion of 2.5 micro g/kg clonidine. The cerebral arteriovenous oxygen content difference (AVDO2) and PaCO2 were sequentially obtained. ICP, PaCO2, AVDO2, and MCAV did not change after clonidine administration. In contrast, MAP and CPP decreased (P < 0.05 and P < 0.05, respectively, at T1 and T2). Three subjects displayed a transient increase in ICP (>10 mm Hg) at T1; this increase was concomitant with the decrease in MAP. Clonidine administered as an IV infusion may induce a critical but transient increase in ICP in some severely head-injured patients. This effect may result from cerebral autoregulatory vasodilation and increased cerebral blood volume as a response to the hypotensive effects of clonidine. (Anesth Analg 1997;84:127-32)

Topical upper airway anaesthesia with lidocaine increases airway resistance by impairing glottic function

ObjectiveTo assess if two different forms of upper airway topical anaesthesia induce similar changes in airway flow resistance (Rrs).DesignSerial measurements of Rrs before and after topical anaesthesia with acqueous or paste lidocaine.SettingLung function test laboratory.Participants9 normal men with documented normal lung function tests.Interventions2 different session of topical upper airway anaesthesia with 100 mg of liquid 5% lidocaine and 100 mg of 2% lidocaine paste, respectively.Measurements and resultsRrs was measured by the random noise forced oscillation technique. Fiberoptic upper airway examination was performed in two subjects. Rrs increased on average by 81% after lidocaine spray and by 68% after lidocaine paste (p<0.005, respectively) with no difference in the magnitude of Rrs increase between the two modes of anaesthesia studied. This increase lasted 13±3 min (spray) and 12±3 min (paste), respectively (p=ns). Fiberoptic examination of the two most responders showed inspiratory laryngeal collapse.ConclusionsTopical upper airway anaesthesia transiently increases Rrs with no specific effects regarding the drug presentation. Laryngeal dysfunction may be one mechanisms involved in Rrs increase following upper airway topical anaesthesia. Such findings may explain some poor respiratory tolerance reported during endoscopy.

TRANSESOPHAGEAL ECHOCARDIOGRAPHIC ASSESSMENT OF LEFT VENTRICULAR FUNCTION DURING APNEA TESTING FOR BRAIN DEATH

The effects of apnea testing-induced respiratory acidosis on left ventricular function (LVF) are still controvenial. The aim of the study was to assess LVF during apnea testing using transesophageal echocardiography (TEE). Twenty consecutive patients suspected of brain death, hemodynamically stable, and considered as potential organ donors were prospectively studied. A 20-min apnea test was performed after obtaining a PaCO2>35 mmHg and 20 min of FIO2 1 ventilation. LVF was assessed using TEE with a CFM 750 (Diasonic) connected to a 5 MHz probe. Heart rate (HR), mean arterial pressure (MAP), left ventricle enddiastolic and systolic area (LVEDA, LVESA), and LVF assessed by fractional area changes (FAC), systolic wall motion (SWM) scores, and blood gases were recorded at baseline, and after 5, 10, 15, and 20 min of apnea testing. In 19 patients, no spontaneous respiratory movement occurred during the standard 20-min period. In one patient (No. 15), the apnea test had to be stopped after 10 min because of hypoxia. HR, LVEDA, LVESA, and SWM were not significantly modified during the study. There was a progressive statistically significant decrease in MAP during apnea (from 77 ±10 to 63±11 mmHg), associated with a statistically significant increase in FAC at 20 min (from 48±13 to 58±8%). PaCO2 progressively rose (from 40±3 to 95±11 mmHg), associated with a decrease in pH (from 7.42±0.06 to 7.09±0.08). At the same time, PaO2 decreased slightly in all patients, but values remained well above hypoxic levels, except for one patient. Despite severe respiratory acidosis the increase in FAC suggests that apnea testing is well tolerated for brain death assessment.

Dissociating anticipation from perception: Acute pain activates default mode network.

Few studies have explored the effect of acute pain on attentional networks and on the default mode network. Moreover, these studies convey conflicting results, seemingly caused by design. To reassess this issue, we studied 20 healthy subjects with functional magnetic resonance imaging while delivering painful electric shocks. The design was purposely constructed to separate rest, anticipation, and pain perception. We found that default mode network activity in response to pain was biphasic. It deactivated during anticipation when the dorsal attentional network was activated. During pain perception, the default mode network was activated, as were attentional networks. The left posterior fusiform gyrus showed the same dynamics as the default mode network, and its activity was negatively correlated to the subjects pain intensity rating. The associative pregenual anterior cingulate cortex seemed to play a key role in these coactivations. These results concur with data from the literature showing that enhanced pain perception results in greater default mode network activity and that the anticorrelation between the default mode network and the dorsal attentional network disappears in chronic pain patients. Hum Brain Mapp 34:2228–2243, 2013.