Octavio Calvillo

Effects of clonidine on narcotic requirements and hemodynamic response during induction of fentanyl anesthesia and endotracheal intubation.

The effects of clonidine, a centrally acting α2-adrenergic receptor agonist, on depth of fentanyl anesthesia and on cardiovascular response to laryngoscopy and intubation were studied. Twenty-four patients undergoing aortocoronary bypass surgery (ACBS) with a history of arterial hypertension, coronary artery disease (NYHA class 3–4), and well-preserved left ventricular function were assigned randomly to either Group 1 (n = 12), who received standard pre-medication, or Group 2 (n = 12), who received clonidine 5 μ;g·kg-1 po in addition to standard premedication 90 min before estimated induction time. Depth of anesthesia was assessed by on-line aperiodic computerized analysis of the electroencephalogram (Lifescan EEG Monitor®). Fentanyl was administered in 250-μ;g increments to shift the EEG to the 0.5–3-Hz frequency range (delta activity) in all subjects. In both groups, the anesthetic regimen effectively prevented hyperdynamic cardiovascular responses to laryngoscopy and intubation. No significant differences in measured or derived hemodynamic variables were observed between the two groups during the awake control period, except for stroke volume index (SVI), which was significantly greater in Group 1,44 ± 9 ml · beat-1 · M-2 compared with Group 2, 35 ± 3.3 ml · beat-1 · m-2 (P < 0.05). By contrast, fentanyl requirements in Group 2 were significantly reduced by 45% when compared with Group 1, i.e., from 110 ± 23 to 61 ± 19 μ;g· kg-1(P < 0.001). The authors conclude that at a similar anesthetic depth, as assessed by the EEG shift into the lower frequency range (0.5–3 Hz), a markedly reduced fentanyl dose effectively prevented the hyperdynamic cardiovascular response to laryngoscopy and intubation in the group of patients premedicated with clonidine. This is likely explained by the known synergistic inhibitory action of opiates and α2-adrenoceptor agonists on central sympathetic outflow.

Anesthesia and hypertension: the effect of clonidine on perioperative hemodynamics and isoflurane requirements

Thirty patients (ASA physical status II-III) with a history of arterial hypertension, whose blood pressure (BP) control varied from normotension to moderate hypertension (diastolic BP < 110 mmHg), scheduled for elective surgery under general anesthesia, were randomly assigned to two groups. Group 1 was premedicated 90–120 min prior to induction with diazepam 0.15 mg · kg1 po; group 2, in addition, received clonidine 5 μg · kg1 po. Anesthetic depth was assessed by on-line aperiodic analysis of the electroencephalogram. Following lidocaine 1 mg · kg1 and fentanyl 2 μg · kg1 (group 1 only), anesthesia was induced with thiopental 3–4 mg · kg1 and vecuronium 0.1 mg · kg1 was used to facilitate endotracheal intubation. Anesthesia was maintained with isoflurane in N2O/O2 and supplemented by fentanyl. In group 2, clonidine produced a rapid preoperative control of systolic and diastolic BP from 166 ± 32/95 ± 14 to 136 ± 80 ± 11 (P < 0.01), was more effective in blunting the reflex tachycardia associated with laryngoscopy and endotracheal intubation than lidocaine-fentanyl pretreatment. It significantly reduced the intraoperative lability (coefficient of variation) of systolic (P < 0.01) and diastolic BP and heart rate (HR) (P < 0.05), and resulted in significantly slower HR during recovery (P < 0.01). Anesthetic requirements for isoflurane were reduced 40% (P < 0.01) in group 2; narcotic supplementation was also significantly reduced (P < 0.005). The authors conclude that these effects of clonidine are explained by the inhibitory action of clonidine on central monoaminergic systems involved in cardiovascular control, modulation of sleep/wake cycle, cortical arousal, and of nociception.

Anesthesia for ophthalmic surgery in the elderly: the effects of clonidine on intraocular pressure, perioperative hemodynamics, and anesthetic requirement.

The effects of clonidine on intraocular pressure and perioperative cardiovascular variables were studied by a randomized double blind design in 80 elderly patients (ASA physical status I-III) scheduled for elective ophthalmic surgery under general anesthesia (GA) and local anesthesia (LA). Group 1 (n = 40), the control group, received diazepam po (0.1 mg·kg-1) 90–120 min prior to arrival to the operating room. Group 2 (n = 40) received clonidine po approximately 5 μg ± kg-1 po at the same time. Each group was divided into subgroups of 20 patients each to be managed with GA (GA subset) or LA (LA subset). Ninety to 120 minutes after the premedication, a large decrease in IOP from 20 ± 3 to 12 ± 3 mmHg (P < 0.01) and a small but significant reduction of both systolic and diastolic BP and HR were observed in patients receiving clonidine, while no changes occurred in controls. In the patients managed with GA, clonidine effectively prevented IOP rise and attenuated the associated cardiovascular response (P < 0.01) following laryngoscopy and tracheal intubation, and significantly reduced intraoperative cardio vascular lability and anesthetic requirement for isoflurane (P < 0.05) and for fentanyl (P < 0.01). In patients managed with LA, intraoperative systolic (P < 0.01) and diastolic BP and HR variability (P < 0.05) were significantly lower in patients receiving clonidine as compared to controls. Intraoperatively, a significantly higher incidence of hypertension (P < 0.01) and tachycardia (P < 0.05) were respectively observed in the LA subset and GA subset of the controls when contrasted with the corresponding subset of those receiving clonidine. Moreover, clonidine was more effective than diazcpam as a premedicaltion; in fact, satisfactory intraoperative sedation and cardiovascular stability were observed in 85% of the patients who received clonidine, and in 50% of those patients who did not receive clonidine (P < 0.01). Thus, clonidine may represent a useful adjunct in the management of the aged patient in the setting of ophthalmic surgery.

Presynaptic effect of clonidine on unmyelinated afferent fibers in the spinal cord of the cat.

The effects of clonidine (Clo) were investigated on the excitability of intraspinal primary afferent terminals of both A- and C-fibers of cutaneous origin. Primary afferent terminal excitability was tested by delivering constant current pulses to the dorsal horn of acutely spinalized cats anesthetized with pentobarbital. Clo given i.v. selectively increased the excitability of the C-fiber primary afferent terminals (mean 85%). Primary afferent terminal excitability of A-fibers was not affected. This effect of Clo was reversed by yohimbine or phentolamine, thus suggesting mediation by alpha2-adrenoceptors. These findings suggest a presynaptic inhibitory effect of Clo in spinal nociceptive pathways that might explain the mechanism of action of this drug.

Thermal grill illusion and complex regional pain syndrome type I (reflex sympathetic dystrophy)

Background and Objectives. In normal humans, placing a hand on a thermal grill containing warm elements separated by cool ones produces a burning sensation. In this case report, responses to a thermal grill in a patient with neuropathic pain were examined. Methods. The responses of a 31‐year‐old woman with complex regional pain syndrome type I (reflex sympathetic dystrophy) to a thermal grill were evaluated before and after stellate ganglion block. Results. The patient experienced a burning sensation when the unaffected hand was placed on the grill and could distinguish which element was warm and which was cool. An intolerable burning sensation caused the patient to quickly (within 4 seconds) withdraw the affected hand when it was placed on the grill. Touching cool elements with the affected hand produced an intense burning sensation (cold allodynia), whereas touching warm elements produced a pleasant warm sensation. Stellate ganglion block with phenol, local anesthetic, and steroid resulted in long‐lasting absence of cold allodynia. Conclusion. The thermal grill may be a useful a tool to help understand the pathophysiology of complex regional pain syndrome type I.

Haemodynamic effects of clonidine injected epidurally in halothane-anaesthetized dogs

The haemodynamic effects of clonidine administered in the epidural space were studied in 16 halothane-anaesthetized dogs. The animals were randomly assigned to two groups; Group I received three doses of 3 ml of normal saline, Group II received three doses of 3 μg·kg-1 of clonidine, through an epidural catheter, whose tip was located between L2-T11. Control haemodynamic measurements were taken one hour after completion of the surgical preparation (period P1); they were repeated every 45 minutes after each incremental dose (periods P2, P3, P4) and 105 minutes after a total cumulative dose of 9 μg·kg-1 of clonidine or 9 ml of saline were given (period P5). No significant changes over time were observed in Group I. In Group II clonidine produced statistically significant reductions of systemic blood pressure (BP), mean left ventricular pressure (LV), heart rate (HR), cardiac output (CO) and peak LV dP/dt only after a total clonidine dose of 9 μg·kg-1 and these changes were sustained. BP fell 15 per cent, CO 21 per cent, HR 25 per cent, LV 20 per cent and peak LV dP/dt 30 per cent when P5 measurements were compared to control values within Group II (p < 0.05). These haemodynamic effects of clonidine are likely due to minimal systemic absorption and/or cephalad spread of the drug towards its site of action in the brain stem. The reductions of HR, CO, BP, and isovolemic indices of contractility are likely explained by a reduction of sympathetic outflow at the spinal cord and medulla oblongata levels as well as increased parasympathetic tone.If these observations can be extrapolated to clinical conditions, in view of the small haemodynamic changes observed only with the highest dose employed, and the potent analgesic effects, epidural administration of clonidine appears safe and may be useful for management of acute postoperative pain.RésuméLes effets hémodynamiques de ľadministration de clonidine dans ľespace épidural étaient étudiés chez 16 chiens anesthésiés à ľhalothane. Les animaux étaient divisés en deux groupes ďune façon randomisée: le groupe I a reçu trois doses de 3 ml de physiologique, le groupe II a reçu trois doses de 3 μg·kg-1 de clonidine, à travers un cathéter épidural dont le bout distal était localisé entre L2 et T11. Les mesures hémo-dynamiques de contrôle étaient prises une heure après ľaccomplissement de la préparation chirurgicale (période P1); elles étaient répétées chaque 45 minutes après chaque dose de rajout (période P2, P3, P4) et 105 minutes après avoir atteint une dose cumulative totale de 9 μg·kg-1 de clonidine ou 9 ml de salin (période P5). Aucun changement significatif à travers le temps n’a été observé dans le groupe I. Dans le groupe II la clonidine a produit une diminution statistiquement significative de la tension artérielle systémique (BP), de la pression du ventricule gauche (LV), de la fréquence cardiaque (HR), du débit cardiaque (CO) et dP/dt maximal uniquement après avoir atteint la dose maximale totale de 9 μg·kg-1. La BP a diminué de 15 pour cent, CO de 21 pour cent, HR de 25 pour cent, LV de 20 pour cent et le dP/dt de 30 pour cent quand les mesures faites au temps P5 étaient comparées aux valeurs de contrôle dans le groupe II (p < 0.05). Ces effets hémodynamiques de la clonidine sont probablement dus à une absorption systémique minime et/ou à une diffusion vers le haut du médicament vers son site ďaction dans le cerveau. La diminution de la fréquence cardiaque, débit cardiaque et la tension artérielle ainsi que les indices isovolumiques de contractilité sont probablement expliqués par une réduction de la réponse sympathique de la moëlle épinière et du bulbe rachidien ainsi qu’une augmentation du tonus parasympathique.Si on pouvait extrapoler ces observations expérimentales aux conditions cliniques et parce que les effets hémodynamiques ont été observés uniquement avec des fortes doses de clonidine qui est un puissant analgésique, ľadministration épidurale de cette drogue apparaît sécuritaire et pourrait être utile au point de vue thérapeutique contre les douleurs aigues postopératoires.

Sympathetic and celiac plexus blocks

Sympathetic blocks are used for the treatment of pain when signs and symptoms of sympathetically maintained pain are present. Additional or alternative treatments are necessary for the care of many patients with complex regional pain syndromes. Celiac plexus blocks are used for the treatment of pain associated with pancreatic cancer and celiac blocks have been shown to have positive results in multiple randomized trials.

Theory and Mechanisms of Action of Neuroaugmentation

Neuroaugmentation techniques are important complementary treatments for the management of chronic pain. Spinal cord stimulation is used to treat patients with chronic radiculitis, complex regional pain syndrome, and ischemic pain.