Conceptual and technical insights into the basis of neuromuscular monitoring.

Unrecognised postoperative residual neuromuscular block remains a frequent occurrence in recovery rooms. Evidence indicates that current practice continues to perpetuate the status quo, in which 10-40% of patients experience postoperative residual weakness. A departure from the current practice requires small efforts on the clinicians' part. This review addresses several selected core questions regarding neuromuscular blockade monitoring and provides a framework to rationally discuss and develop basic guidelines for the use of neuromuscular blocking agents in patient care.

Effect of lidocaine on endothelin-1-mediated airway smooth muscle contraction in the rat trachea.

BACKGROUND: Endothelin-1 (ET-1) is a 21-amino acid peptide that induces airway smooth muscle (ASM) constriction by activating G-protein-coupled endothelin receptors A (ETA) and B (ETB), thereby increasing intracellular calcium ([Ca(2+)]i). Lidocaine can cause direct ASM relaxation by decreasing [Ca(2+)]i. This study investigated the direct relaxant effects of lidocaine on ET-1-induced contraction in rat tracheas. METHODS: Mid-tracheal rings (2-3 mm diameter) were excised and attached to a force transducer suspended in Krebs-Henseliet solution. Carbachol concentration-response curves (10 nM and 100 microM) were generated to determine maximal contractility (C(max)). ET-1 (3 nM to 200 nM) responses to lidocaine (100 nM, 10 microM, and 1 mM) were measured in the presence and absence of extracellular calcium. Contractile responses to ET-1 are presented as percentage of Cmax (% Cmax). Data were analyzed using analysis of variance and unpaired t-tests with Welsh correction. RESULTS: No significant effect on ET-1-induced constriction was noted in the presence of low concentrations of lidocaine (100 nM and 1 muM), with and without extracellular calcium. At a concentration of 1 mM, lidocaine decreased the response to 100 nM and 200 nM ET-1 by 26% in the presence of extracellular calcium and by 37 and 44%, respectively, in the absence of calcium. CONCLUSION: The attenuating effect of lidocaine (1 mM) on ET-1-induced ASM contraction is not exclusively dependent on the blockade of intracellular calcium entry.

Combined spinal-epidural analgesia for labor in a patient with Marfan's syndrome.

We report the management of a patient with Marfan's syndrome for labor analgesia and vaginal delivery using a combined spinal-epidural technique. The rapid onset of analgesia for the first stage of labor provided by the intrathecal opioid, combined with the slow and controlled onset of sensory anesthesia and sympathetic block provided by the dilute epidural local anesthetic, may make this technique particularly useful for labor and delivery in patients with Marfan's syndrome.

The effect of desflurane on rocuronium onset, clinical duration and maintenance requirements.

Volatile anesthetics potentiate the effects of non-depolarizing agents. This study investigated the interaction between the inhalational anesthetic desflurane and rocuronium. Forty ASA I and II patients randomly received desflurane/N2O/fentanyl, or propofol/ N2O/fentanyl anesthesia, and rocuronium 0.6 mg/kg. Neuromuscular block was assessed at the adductor pollicis muscle. Block onset and clinical duration times were measured; a rocuronium infusion was started when the first twitch on train-of-four returned to 10% of control (T10%). Maintenance infusion requirements and recovery profiles (spontaneous and after reversal) were recorded until recovery of twitch to 90% of control (T90%). Rocuronium onset was prolonged by 67% (p = 0.034), clinical duration by 30% (p = NS), and infusion requirements were lower in the desflurane group (4.5 vs. 7.1 mg/kg/min, p = 0.003). Recovery times were not statistically different. Desflurane significantly delays the onset of neuromuscular block, potentiates rocuronium during maintenance infusion, but does not affect clinical duration or recovery.

Haemodynamic changes induced by hyperbaric bupivacaine during lateral decubitus or supine spinal anaesthesia.

BACKGROUND AND OBJECTIVE: Hypotension, the commonest side-effect of spinal anaesthesia, results from sympathetic denervation. This study compared patient positioning (supine vs. decubitus) on haemodynamic variables during spinal anaesthesia. METHODS: After intravenous crystalloid preloading with 5 mL kg(-1), hyperbaric bupivacaine 0.5% 2.5 mL was injected intrathecally at the L2-3 or L3-4 interspace. Patients were then randomly assigned to be positioned immediately supine and horizontal for 30 min (Group SUP, n = 12), or remained in the lateral decubitus position (fractured hip dependent) for 30 min (Group LAT, n = 14). Systolic blood pressure, mean arterial pressure, and loss of sensation of pinprick sensation were recorded prior to induction of spinal anaesthesia (baseline) and at 1, 2, 3, 5, 10, 15, 30, 45, 60, 90 and 120 min after intrathecal injection. RESULTS: In Group SUP, the percent maximum systolic blood pressure (36 +/- 13%) and percent maximum mean arterial pressure decreases (27 +/- 13%) were significantly greater (P < 0.05) than in Group LAT (30 +/- 8% and 23 +/- 11%, respectively). Additionally, there was a borderline significant delay in the time to maximum systolic blood pressure decrease in Group LAT (38 +/- 30 min) when compared with Group SUP (20 +/- 17 min, P = 0.06), while the total dose of ephedrine required in the SUP group (30 mg) was greater than that required in the LAT group (15 mg, P = 0.05). In Group LAT patients, the mean level of denervation on the operative side extended 2 dermatomes more cephalad than in Group SUP. CONCLUSIONS: Lateral positioning for spinal anaesthesia delays the onset of hypotension, while requiring smaller total doses of vasoconstrictors for blood pressure maintenance.

Preemptive analgesia II: recent advances and current trends.

PURPOSE: This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia. SOURCE: Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents. PRINCIPAL FINDINGS: In Part I of this review article, techniques and agents that attenuate or prevent central and peripheral sensitization were reviewed. In Part II, the conditions required for effective preemptive techniques are evaluated. Specifically, preemptive analgesia may be defined as an antinociceptive treatment that prevents establishment of altered central processing of afferent input from sites of injury. The most important conditions for establishment of effective preemptive analgesia are the establishment of an effective level of antinociception before injury, and the continuation of this effective analgesic level well into the post-injury period to prevent central sensitization during the inflammatory phase. Although single-agent therapy may attenuate the central nociceptive processing, multi-modal therapy is more effective, and may be associated with fewer side effects compared with the high-dose, single-agent therapy. CONCLUSION: The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input require individualization of the technique(s) chosen. Multi-modal analgesic techniques appear more effective.

Preemptive analgesia I: physiological pathways and pharmacological modalities.

PURPOSE: This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia. SOURCE: Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents. PRINCIPAL FINDINGS: The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (N-methyl-D-aspartate) - and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain. CONCLUSION: The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.

Topical application of acidic bupivacaine to the lumbar ganglion induces mechanical hyperalgesia in the rat.

UNLABELLED: To investigate the neurologic mechanisms of acidic local anesthetic-induced low back pain in humans, we administered bupivacaine and buffered saline at acidic or alkalinized pH at the L5 dorsal root ganglion (DRG) of rats via a hole drilled through the transverse process covering the DRG. Behavioral changes were tested before and after bupivacaine or saline administration. Results indicate that acute single-dose infusion of the DRG with bupivacaine (0.5%) at acidic pH (5.5) induced ipsilateral mechanical hyperalgesia that lasted for 7 days. Acute infusion of alkalinized bupivacaine (pH 7.2), however, caused only minor hyperalgesia that lasted <3 days. Similar results were obtained when bupivacaine was replaced with saline. Alternatively, chronic delivery of acidic saline to the DRG via a subcutaneously implanted osmotic pump resulted in a significant decrease in the withdrawal threshold on the ipsilateral hind paw that lasted for 10 days. In rats receiving chronic treatment of the DRG with alkalinized saline, mechanical hyperalgesia lasted for only 3 days. The results demonstrated that acidic bupivacaine deposited at the DRG causes pain and hyperalgesia when the effects of the local anesthetic have dissipated. These findings may explain the limited therapeutic effects of some acidic local anesthetics used for management of cancer-related and chronic back pain. IMPLICATIONS: Acidic bupivacaine administered at the L5 lumbar ganglion causes pain and hypersensitivity of the hind paw in the rat. These findings may explain the limited therapeutic effects of some acidic local anesthetics used for treatment of cancer-related and chronic back pain.

Effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents of the dorsal horn neurons in newborn rats.

BACKGROUND: Local anesthetics, such as bupivacaine, have been reported to block calcium currents in primary sensory neurons and to interfere with the release of neurotransmitters in central nervous system neurons. However, it is unknown whether local anesthetics affect the calcium current activity of central nervous system neurons. METHODS: Using a traditional whole cell voltage clamp technique, effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents (HVA-Ic(a)) were investigated in enzymatically dissociated dorsal horn neurons of neonatal rats. Calcium currents were evoked by testing pulses from a holding potential of -90 to 0 mV. RESULTS: Bupivacaine significantly reduced HVA-Ic(a) in a dose-dependent manner. The peak HVA-Ic(a) decreased by 24.5+/-2.5, 32.0+/-6.8, 59.4+/-6.2, 88.3+/-1.5, and 91.6+/-1.1% in response to 10, 30, 50, 100 and 200 microM bupivacaine, respectively. Unlike bupivacaine, ropivacaine markedly increased HVA-Ic(a) at lower concentrations (< 50 microM) but decreased HVA-Ic(a) at higher concentrations (> or = 50 microM). The percent increases in peak HVA-Ic(a) induced by 10 and 30 microM ropivacaine were 95+/-19.1 and 41.6+/-8.3%, respectively. The percent decreases in response to 50, 100, and 200 microM ropivacaine were 21.1+/-2.1, 63.2+/-6.0 and 79.1+/-7.6%, respectively. Results indicate that the inhibitory potency of ropivacaine on HVA-Ic(a) was significantly lower than that of bupivacaine at the same concentrations. CONCLUSIONS: The current study showed that bupivacaine inhibited HVA-Ic(a) recorded from dorsal horn neurons and that ropivacaine increased HVA-Ic(a) at lower concentrations but decreased HVA-Ic(a) at higher concentrations. The inhibitory potency of ropivacaine was lower than that of bupivacaine. Inhibition of calcium currents of central nervous system neurons may be related to the systemic neurotoxic effects of local anesthetics (e.g., convulsions, seizures).

Perfusion of the mechanically compressed lumbar ganglion with lidocaine reduces mechanical hyperalgesia and allodynia in the rat.

The rat L(5) dorsal root ganglion (DRG) was chronically compressed by inserting a hollow perforated rod into the intervertebral foramen. The DRG was constantly perfused through the hollow rod with either lidocaine or normal saline delivered by a subcutaneous osmotic pump. Behavioral evidence for neuropathic pain after DRG compression involved measuring the incidence of hindlimb withdrawals to both punctate indentations of the hind paw with mechanical probes exerting different bending forces (hyperalgesia) and to light stroking of the hind paw with a cotton wisp (tactile allodynia). Behavioral results showed that for saline-treated control rats: the withdrawal thresholds for the ipsilateral and contralateral paws to mechanical stimuli decreased significantly after surgery and the incidence of foot withdrawal to light stroking significantly increased on both ipsilateral and contralateral hind paws. Local perfusion of the compressed DRG with 2% lidocaine for 7 days at a low flow-rate (1 microl/h), or for 1 day at a high flow-rate (8 microl/h) partially reduced the decrease in the withdrawal thresholds on the ipsilateral foot but did not affect the contralateral foot. The incidence of foot withdrawal in response to light stroking with a cotton wisp decreased significantly on the ipsilateral foot and was completely abolished on the contralateral foot in the lidocaine treatment groups. This study demonstrated that compression of the L(5) DRG induced a central pain syndrome that included bilateral mechanical hyperalgesia and tactile allodynia. Results also suggest that a lidocaine block, or a reduction in abnormal activity from the compressed ganglia to the spinal cord, could partially reduce mechanical hyperalgesia and tactile allodynia.

Comparison of ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in volunteers.

UNLABELLED: A longer acting local anesthetic such as ropivacaine may offer advantages over lidocaine for IV regional anesthesia (IVRA). The objective of this investigation was to determine whether the use of ropivacaine improves the quality and duration of IVRA. In a randomized, double cross-over design, 10 volunteers received lidocaine 0.5% or ropivacaine 0.2% for IVRA of the upper extremity on two separate days with a standard double-cuff technique. Sensation to pinprick, response to tetanic stimuli, and tourniquet pain were assessed on a 0-10 verbal numeric score scale at 5-min intervals throughout the period of tourniquet inflation. Motor function was evaluated by grip strength. After release of the second (distal) cuff, pinprick sensation, motor strength, and systemic side effects were evaluated at 3, 10, and 30 min. No significant differences were observed for onset times of anesthesia and times to proximal (38 +/- 3 and 36 +/- 3 min) or distal (34 +/- 13 and 36 +/- 13 min) tourniquet release after the administration of ropivacaine and lidocaine, respectively. However, postdeflation hypoalgesia and motor blockade were prolonged with ropivacaine, and postdeflation light-headedness, tinnitus, and drowsiness were more prominent with lidocaine. We conclude that ropivacaine may be an alternative to lidocaine for IVRA. It may result in prolonged analgesia and fewer side effects after tourniquet release. IMPLICATIONS: In this study, volunteers received lidocaine 0.5% or ropivacaine 0.2% for IV regional anesthesia on two study days. Ropivacaine and lidocaine provided similar surgical conditions. However, after release of the distal tourniquet, prolonged sensory blockade and fewer central nervous system side effects were observed with ropivacaine.

The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery.

UNLABELLED: Patients undergoing vascular surgery have a high risk of suffering major postoperative cardiac events. Preoperative myocardial ischemia as detected by Holter monitoring identifies a high-risk subgroup whose postoperative ischemia, similarly detected, seems to herald major cardiac events. In this study, we determined whether systematic, patient-specific postoperative heart rate control with beta-adrenergic blocker therapy decreases the incidence of postoperative ischemia among high-risk vascular surgery patients. A total of 26 of 150 patients who underwent elective vascular surgery and were monitored preoperatively by 24-h Holter were found to have significant myocardial ischemia as defined by ST-segment depression. The minimal heart rate at which this ST-segment depression occurred was identified (ischemic threshold), and these 26 patients were then randomized to receive continuous i.v. beta-blockade with esmolol or placebo plus usual medical therapy, aiming to reduce the postoperative heart rate to 20% below the ischemic threshold. All patients were monitored by Holter for 48 h postoperatively. Postoperative Holter readings were analyzed for the incidence of ischemia and for the number of hours during which heart rate was controlled below the ischemia threshold. Patients had a median of two episodes of preoperative ischemia lasting a median of 30 min (range 1-155 min). A total of 15 patients were randomized to receive esmolol, and 11 were randomized to receive placebo. The two groups were comparable with respect to clinical characteristics and incidence and duration of preoperative ischemia. Ischemia persisted in the postoperative period in 8 of 11 placebo patients (73%), but only 5 of 15 esmolol patients (33%) (P < 0.05). Of the 15 esmolol patients, 9 had mean heart rates below the ischemic threshold, and all 9 had no postoperative ischemia. A total of 4 of 11 placebo patients had mean heart rates below the ischemic threshold, and 3 of the 4 had no postoperative ischemia. There were two postoperative cardiac events among patients who had postoperative ischemia (one placebo, one esmolol) and whose mean heart rates exceeded the ischemic threshold. Our data suggest that patient-specific, strict heart rate control aiming for a predefined target based on individual preoperative ischemic threshold was associated with a significant reduction and frequent elimination of postoperative myocardial ischemia among high-risk patients and provide a rationale for a larger trial to examine this strategy's effect on cardiac risk. IMPLICATIONS: Patients who undergo peripheral vascular surgery often experience transient cardiac complications and/or permanent heart damage just after surgery because of inadequate myocardial blood flow. In this study, we identified patients at high risk of cardiac complications after vascular surgery and showed that if their heart rate was carefully controlled for 48 h after surgery, myocardial ischemia, a common marker of heart injury, was markedly reduced.

A method for overcoming the ceiling effect of bounded pain scales.

OBJECTIVE: The Verbal Numerical Scale (VNS) for rating pain is bounded between 0 (= no pain) and 10 (= worst pain imaginable). We hypothesized that the limitations inherent to this boundary when rating extremely painful stimuli may be identified by integrating the VNS with an unbounded score such as magnitude estimation of relative change. METHODS: Volunteers received stimuli of increasing current via cutaneous electrodes until they rated >5 on the VNS scale. This stimulus, termed S, was arbitrarily assigned a magnitude estimate of 100%. Then, stimuli of varying currents were delivered; two were 10 mA and 20 mA higher than S (S(+10) and S(+20)), two were 1/2 of the current for the S stimulus (S(1/2)), and one was at the original current (Srepeat). The pain elicited by each stimulus was scored in proportion to the S stimulus. The extrapolated VNS score (VNSext) was determined by multiplying this magnitude estimate (%) by the VNS score for S. MAIN RESULTS: Seventy percent of the stimuli with higher intensity than S generated a VNSext score above 10. The mean magnitude estimations for S(+10) and S(+20) were 186% and 242%: they generated mean (median) VNSext values of 12.4 and 16.2, respectively (p = 0.019 for the difference between them by Wilcoxon signed rank test). CONCLUSIONS: The combined use of VNS and magnitude estimation confirmed that the ceiling of the bounded pain scale may significantly limit a patient's ability to describe a new pain stimulus. VNSext may provide a means of overcoming this limitation.