Local anaesthetic-induced myotoxicity in regional anaesthesia: a systematic review and empirical analysis.

Recent reports of local-anaesthetic (LA)-induced myotoxicity after peripheral nerve blocks have increased the interest in this less commonly known complication. Basic science evidence investigating LA-induced myotoxicity seems to demonstrate a pattern, but findings from human studies vary. This systematic review summarises the existing myotoxicity evidence and empirically examines its implications. Databases were searched for all in vitro animal and human studies evaluating LA-induced myotoxicity. Studies were stratified by design. Data sought included the model examined, LA used, injury mechanisms, nature of damage, and extent of recovery. For human studies, we also aimed to estimate prevalence and recovery rates. One hundred and fifteen studies, mainly animal and ophthalmic, were included. Myotoxicity risk factors included higher concentrations and prolonged exposure to LA, and use of bupivacaine. Injury mechanisms involved early and late aberrations to cytoplasmic calcium (Ca2+) homeostasis by the sarcoplasmic reticulum Ca2+ ATPase. Incidence in ophthalmic studies was 0.77% (392 of 50 618). Inflammatory changes within a few days after exposure marked the onset of myotoxicity, and myo-degeneration followed within the first week post-exposure. Time to recovery in human muscles ranged between 4 days to 1 yr. None/partial and complete recovery were observed in 61% and 38% of patients, respectively. Across all experimental models, skeletal muscles exposed to LA consistently display myotoxic effects. Evidence is robust in animal and ophthalmic studies, and displays a concerning signal with continuous adductor canal block use in human case reports. Exploring the clinical prevalence, severity, and risk-reducing strategies of myotoxicity should be prioritised.

Hospital discharge after ambulatory knee arthroscopy: A comparison of epidural 2-chloroprocaine versus lidocaine.

BACKGROUND AND OBJECTIVES: This prospective, randomized, double-blind study compares the efficacy of epidural 2-chloroprocaine and lidocaine for attaining hospital discharge criteria after ambulatory knee arthroscopy. We hypothesized that 2-chloroprocaine would facilitate earlier discharge than lidocaine. METHODS: American Society of Anesthesiologists (ASA) I and II patients were randomized to receive equipotent doses of epidural 3% 2-chloroprocaine or 1.5% lidocaine, both without epinephrine. Time to block resolution and discharge were compared between groups, along with the need for epidural reinjection, surgical times, and postoperative back pain. RESULTS: Twenty-seven patients completed the study, 13 in the 2-chloroprocaine group and 14 in the lidocaine group. The 2-chloroprocaine group was ready for discharge significantly earlier than the lidocaine group (130 +/- 17 min [range, 105 to 160] v 191 +/- 32 min [range 144 to 251]; P <.0001, 90% power). The lidocaine group required more epidural reinjections. Anesthesia-related side effects were similar in both groups. CONCLUSIONS: Epidural 3% 2-chloroprocaine without epinephrine is an advantageous choice for ambulatory knee arthroscopy. It enables readiness for discharge an hour sooner than 1.5% lidocaine, requires fewer reinjection interventions, and may reduce delayed discharge secondary to prolonged time to void. This clinical study shows the superiority of epidural 3% 2-chloroprocaine over 1.5% lidocaine for expediting hospital discharge after ambulatory surgery.

Sedation during spinal anesthesia.

BACKGROUND: Central neuraxial anesthesia has been reported to decrease the dose of both intravenous and inhalational anesthetics needed to reach a defined level of sedation. The mechanism behind this phenomenon is speculated to be decreased afferent stimulation of the reticular activating system. The authors performed a two-part study (nonrandomized pilot study and a subsequent randomized, double-blind, placebo-controlled study) using the Bispectral Index (BIS) monitor to quantify the degree of sedation in unmedicated volunteers undergoing spinal anesthesia. METHODS: Twelve volunteers underwent BIS monitoring and observer sedation scoring (Observer's Assessment of Alertness/Sedation Scale [OAA/S]) before and after spinal anesthesia with 50 mg hyperbaric lidocaine, 5%. Subsequently, 16 volunteers blinded to the study were randomized to receive spinal anesthesia with 50 mg hyperbaric lidocaine, 5% (n = 10) or placebo (n = 6) and underwent BIS and OAA/S monitoring. RESULTS: In part I, significant changes in BIS scores of the volunteers occurred progressively (P = 0.003). The greatest variations from baseline BIS measurement occurred at 30 and 70 min. In part II, there were significant decreases in OAA/S and self-sedation scores for patients receiving spinal anesthesia versuscontrol patients (P = 0.04 and 0. 01, respectively). The greatest decrease in OAA/S scores occurred at 60 min. BIS scores were similar between groups (P = 0.4). CONCLUSIONS: Spinal anesthesia is accompanied by significant sedation progressively when compared with controls as measured by OAA/S and self-sedation scores. This effect was not related to block height. The late sedation observed by OAA/S at 60 min may indicate a second mechanism of sedation, such as delayed rostral spread of local anesthetics. BIS was not a sensitive measure of the sedation associated with spinal anesthesia in the randomized, blinded portion of this study.

Procaine compared with lidocaine for incidence of transient neurologic symptoms.

BACKGROUND AND OBJECTIVES: Transient neurologic symptoms (TNS) have been reported to occur after 16% to 40% of ambulatory lidocaine spinal anesthetics. Patient discomfort and the possibility of underlying lidocaine neurotoxicity have prompted a search for alternative local anesthetic agents. We compared the incidence of TNS with procaine or lidocaine spinal anesthesia in a 2:1 dose ratio. METHODS: Seventy outpatients undergoing knee arthroscopy were blindly randomized to receive either 100 mg hyperbaric procaine or 50 mg hyperbaric lidocaine. An interview by a blinded investigator established the presence or absence of TNS, defined as pain in the buttocks or lower extremities beginning within 24 hours of surgery. Onset of sensory and motor block, patient discomfort, supplemental anesthetics, and side effects were recorded by the unblinded managing anesthesia team. Anesthetic adequacy was determined from these data by a single blinded investigator. Hospital discharge time was recorded from the patient record. Groups were compared using appropriate statistics with a P < .05 considered significant. RESULTS: TNS occurred in 6% of procaine patients versus 31% of lidocaine patients (P = .007). Sensory block with procaine and lidocaine was similar, while motor block was decreased with procaine (P < .05). A trend toward a higher rate of block inadequacy (17% v 3%, P = .11) and intraoperative nausea (17% v 3%, P = .11) occurred with procaine. Average hospital discharge time with procaine was increased by 29 minutes (P < .05). CONCLUSIONS: The incidence of TNS was substantially lower with procaine than with lidocaine. However, procaine resulted in a lower overall quality of anesthesia and a prolonged average discharge time. If the shortfalls of procaine as studied can be overcome, it may provide a suitable alternative to lidocaine for outpatient spinal anesthesia to minimize the risk of TNS.

Spinal nerve function in five volunteers experiencing transient neurologic symptoms after lidocaine subarachnoid anesthesia.

UNLABELLED: The etiology of transient neurologic symptoms (TNS) after 5% lidocaine spinal anesthesia remains undetermined. Previous case reports have shown that patients acutely experiencing TNS have no abnormalities on neurologic examination or magnetic resonance imaging. The aim of our study was to determine whether volunteers with TNS would exhibit abnormalities in spinal nerve electrophysiology. Twelve volunteers with no history of back pain or neurologic disease underwent baseline electromyography (EMG), nerve conduction studies, and somatosensory-evoked potential (SSEP) testing. Then, the volunteers were administered 50 mg of 5% hyperbaric lidocaine spinal anesthesia and were placed in a low lithotomy position (legs on four pillows). The next day, all volunteers underwent follow-up EMG, nerve conduction, and SSEP testing and were questioned and examined for the presence of complications including TNS (defined as pain or dysthesia in one or both buttocks or legs occurring within 24 h of spinal anesthesia). Volunteers who had TNS underwent additional EMG testing 4-6 wk later. Five of the 12 volunteers reported TNS. No volunteer had an abnormal EMG, nerve conduction study, or SSEP at 24 h follow up, nor were there any changes in EMG studies at delayed testing in the five volunteers experiencing TNS. On statistical analysis, the right peroneal and the right tibial nerve differed significantly for all volunteers from pre- to postspinal testing. When comparing pre- and postspinal testing of the TNS and non-TNS volunteers, statistically significant changes occurred in the nerve conduction tests of the right peroneal and left tibial nerve. There was no difference in measurements of F response, H reflex latency, amplitude, or velocity for either leg. Multivariate analysis of variance showed no significant difference between TNS and non-TNS volunteers for the changes in the nine nerve conduction tests when considered together (P = 0.4). We conclude that acute TNS after lidocaine spinal anesthesia did not result in consistent abnormalities detectable by EMG, nerve conduction studies, or SSEP in five volunteers. IMPLICATIONS: Electrophysiologic testing in volunteers experiencing transient neurologic symptoms is not abnormal.

Successful pregnancy in a woman with acromegaly treated with octreotide.

OBJECTIVE: To report a successful pregnancy in a 43-year-old woman with acromegaly and treatment during pregnancy with the somatostatin analogue octreotide, to review the physiologic aspects of acromegaly during pregnancy, and to discuss treatment options. METHODS: A case report is presented, and the current literature is reviewed. RESULTS: In a 40-year-old woman with acromegaly and secondary amenorrhea, menstrual periods resumed after treatment with octreotide. At age 43 years, she became pregnant and decided to continue octreotide therapy because of the relatively large size of the tumor and severe headaches when use of the medication was discontinued. Growth hormone and insulin-like growth factor I levels remained normal throughout pregnancy, and a normal full-term infant was born. Several months after delivery, severe cholecystitis developed, and the patient underwent laparoscopic cholecystectomy. CONCLUSIONS: This case report describes the oldest documented woman with acromegaly who has completed a pregnancy and only the second patient treated with octreotide for the entire pregnancy. During a normal pregnancy, placental growth hormone suppresses pituitary growth hormone secretion; in patients with acromegaly, pituitary growth hormone secretion remains autonomous. Treatment of acromegaly with octreotide, bromocriptine, irradiation, or surgical intervention may restore menses and fertility to women of reproductive age. Bromocriptine has been used throughout pregnancy without teratogenic effects in many patients. Octreotide has been used during the first trimester of pregnancy in seven other women with acromegaly (throughout pregnancy in one of those patients) and for the entire pregnancy in one woman with a thyrotropin-secreting pituitary tumor; no adverse effects were noted. Lanreotide was also used in one patient briefly during the first trimester without adverse consequences. Although the outcomes of the current and previous pregnancies have been favorable, insufficient data are available to recommend the routine use of octreotide in all pregnant women with acromegaly.

The neurotoxicity of drugs given intrathecally (spinal)

Overall, most spinal drugs in clinical use have been poorly studied for spinal cord and nerve root toxicity. Laboratory studies indicate that all local anesthetics are neurotoxic in high concentrations and that lidocaine and tetracaine have neurotoxic potential in clinically used concentrations. However, spinal anesthesia (including lidocaine and tetracaine) has a long and enviable history of safety. Spinal analgesics such as morphine, fentanyl, sufentanil, clonidine, and neostigmine seem to have a low potential for neurotoxicity based on laboratory and extensive clinical use. Most antioxidants, preservatives, and excipients used in commercial formulations seem to have a low potential for neurotoxicity. In addition to summarizing current information, we hope that this review stimulates future research on spinal drugs to follow a systematic approach to determining potential neurotoxicity. Such an approach would examine histologic, physiologic, and behavioral testing in several species, followed by cautious histologic, physiologic, and clinical testing in human volunteers and patients with terminal cancer refractory to conventional therapy.

Dilution of spinal lidocaine does not alter the incidence of transient neurologic symptoms.

BACKGROUND: Although it has been suggested that the dilution of 5% hyperbaric lidocaine before injection for spinal anesthesia may decrease the incidence of transient neurologic symptoms, previous studies have not noted a decreased incidence between 5% and 2% lidocaine. The aim of the current study was to determine whether the incidence of transient neurologic symptoms could be altered by further diluting spinal lidocaine from 2.0% to 0.5%. METHODS: One hundred nine patients with American Society of Anesthesiologists physical status 1 or 2 undergoing outpatient knee arthroscopy were randomized in a double-blind fashion to receive 50 mg hyperbaric spinal lidocaine as a 2.0%, 1.0%, or 0.5% concentration. On the third postoperative day, patients were contacted by a blinded investigator and questioned regarding the incidence of postoperative complications, including transient neurologic symptoms, defined as pain or dysthesia in one or both buttocks or legs occurring within 24 h of surgery. RESULTS: The incidence of transient neurologic symptoms did not differ among patients receiving 2.0% (incidence of 15.8%), 1.0% (incidence of 22.2%), and 0.5% (incidence of 17.1%) lidocaine (P = 0.756). CONCLUSIONS: For ambulatory patients undergoing arthroscopy, the incidence of transient neurologic symptoms is not reduced by decreasing spinal lidocaine concentrations from 2.0% to 1.0% or 0.5%. The incidences of transient neurologic symptoms with the 0.5%, 1.0%, and 2.0% solutions are similar to previously reported incidences for 5.0% lidocaine, suggesting that dilution of lidocaine from 5.0% to 0.5% does not change the incidence of these symptoms.

Quantitative analysis of respiratory, motor, and sensory function after supraclavicular block.

UNLABELLED: The incidence and clinical significance of hemidiaphragmatic paresis after supraclavicular block of the brachial plexus is unknown. Eight healthy volunteers received a supraclavicular block with a standard technique using 30 mL of 1.5% lidocaine. Respiratory function was assessed with ultrasound of the diaphragm, respiratory inductive plethysmography (RIP), and pulmonary function tests (PFT) every 20 min. Sensory block was assessed with pinprick and motor block with isometric force dynamometry every 20 min. Four of eight subjects demonstrated hemidiaphragmatic paresis on both ultrasound and RIP. No subject experienced changes in PFT values or subjective symptoms of respiratory difficulty. Motor and sensory blockade outlasted hemidiaphragmatic paresis. These results are contrasted to the often symptomatic, 100% incidence of hemidiaphragmatic paresis seen after interscalene block. In this study of healthy volunteers, supraclavicular block was associated with a 50% incidence (95% confidence interval 14-86) of hemidiaphragmatic paresis that was not accompanied by clinical evidence of respiratory compromise. IMPLICATIONS: Interscalene block is always associated with diaphragmatic paralysis and respiratory compromise. The significance of these side effects after supraclavicular block is unknown. Using sensitive measures of respiratory function, we determined that diaphragmatic paralysis occurs less often with the supraclavicular approach and is not associated with respiratory difficulties in healthy subjects.

The effect of epinephrine on small-dose hyperbaric bupivacaine spinal anesthesia: clinical implications for ambulatory surgery.

UNLABELLED: The effect of adding epinephrine to small doses of spinal bupivacaine on the duration of sensory motor block has not been carefully investigated. Twelve volunteers underwent hyperbaric bupivacaine spinal anesthesia (7.5 mg) with and without epinephrine (0.2 mg) in a randomized, double-blind, cross-over fashion. Sensory block was assessed with pinprick, transcutaneous electrical stimulation (TES) equivalent to surgical stimulation (at umbilicus, pubis, knee, and ankle), and tolerance of a pneumatic thigh tourniquet. Motor block was assessed with isometric force dynamometry. Discharge criteria were defined as return of pinprick sensation to dermatome S2, ability to ambulate, and ability to urinate. Extent of sensory block to pinprick over time was unaffected by the addition of epinephrine. However, epinephrine prolonged tolerance of TES at the pubis, knee, and ankle (33-48 min, P < 0.05) and of thigh tourniquet (30 min, P < 0.01). Motor block was prolonged by epinephrine at the quadriceps and gastrocnemius muscles (by 23 and 51 min, respectively, P < 0.002). Achievement of discharge criteria was prolonged by 48 min by the addition of epinephrine (P < 0.01). Thus, epinephrine may prolong surgical anesthesia for lower abdominal and lower extremity surgery and delay time until patients achieve discharge criteria. IMPLICATIONS: Using a cross-over study design, 12 volunteers underwent bupivacaine spinal anesthesia with and without epinephrine. This study suggests that adding epinephrine to bupivacaine may prolong surgical anesthesia and also delay patients' discharge.

Premedication with fentanyl and midazolam decreases the reliability of intravenous lidocaine test dose.

UNLABELLED: This study was performed to determine whether premedication with midazolam and fentanyl prevents reliable detection of an i.v. lidocaine test dose. Thirty ASA physical status I or II patients received either 3 mL of saline or 1.5 mg of midazolam (1.5 mL) plus 75 microg of fentanyl (1.5 mL) i.v. in a randomized, double-blind fashion. Five minutes later, lidocaine 1 mg/kg was injected i.v. At 1.5 min before and every minute after lidocaine administration, each subject was questioned regarding the presence of four symptoms of systemic lidocaine toxicity. Any new tinnitus, perioral numbness, metallic taste, or light-headedness within 5 min after lidocaine administration was considered a positive response. All 15 patients in the saline group (100% sensitivity) had a positive response to i.v. lidocaine, but only 9 of 15 patients in the sedation group had a positive response (60% sensitivity; P = 0.017). We conclude that midazolam and fentanyl premedication decreases the reliability of subjective detection of i.v. lidocaine. IMPLICATIONS: Anesthesiologists often rely on subjective symptoms to prevent local anesthetic toxicity while performing regional anesthesia. Sedatives are often administered during the administration of regional anesthesia. This study demonstrates that typical sedation decreases the reliability of detection of local anesthetic toxicity by subjective symptoms.

2-Chloroprocaine and bupivacaine are unreliable indicators of intravascular injection in the premedicated patient.

BACKGROUND AND OBJECTIVES: Epinephrine-containing test doses for detection of intravascular injection during epidural anesthesia may be unreliable or hazardous in beta-blocked, elderly, or pregnant patients. Subtoxic injections of lidocaine have been used as an alternative marker of intravascular injection in unpremedicated patients. We studied two groups of premedicated patients and unpremedicated subjects to evaluate the reliability of the local anesthetics bupivacaine (B) and 2-chloroprocaine (2-CP) as test dose injections. METHODS: Thirty ASA I and II subjects received blinded randomized injections of 2-CP, B, or normal saline via a peripheral vein. RESULTS: In group I, 10 healthy unpremedicated volunteers universally recognized injection of 90 mg 2-CP or 25 mg B, but did not reliably detect the injection of 60 mg 2-CP. In group II, 20 patients premedicated with 1 microg/kg fentanyl and 30 microg/kg midazolam could not reliably detect similar injections. Sixteen responded to the injection of 90 mg 2-CP, while 13 detected the 25 mg B test dose. A blinded observer rated only 12 of the subjective reports as conclusive of detection of intravascular injection after each drug. There were no false-positive reports in any group. CONCLUSIONS: While 90 mg 2-CP or 25 mg B may be reliable alternatives to epinephrine test doses in unpremedicated subjects, they are unreliable indicators of intravascular injection in the premedicated patient.

Euthyroid pretibial myxedema.

OBJECTIVE: To describe a case of biopsy-proven pretibial myxedema in a man with normal thyroid function. METHODS: We present the pertinent clinical and laboratory data for the current case and review previously published information on pretibial myxedema. RESULTS: Our patient, a 53-year-old man, had the characteristic lesions of pretibial myxedema on the anterolateral aspects of his calves. Laboratory tests showed normal thyroid function. The thyroid-stimulating immunoglobulin value was above normal. No exophthalmos or goiter was present. This uncommon dermopathy is typically associated with Graves' disease, accompanied by clinical hyperthyroidism, ophthalmopathy, and goiter. CONCLUSION: The pathogenesis of pretibial myxedema remains elusive. It is presumed to be an autoimmune phenomenon attributable to the presence of serum thyroid-stimulating immunoglobulin, although immunofluorescence studies have failed to demonstrate a direct role for such an immunoglobulin. Only two other cases of biopsy-proven pretibial myxedema in a euthyroid patient were found in the literature.

A collaborative approach to minimally invasive direct coronary artery bypass.

Minimally invasive direct coronary artery bypass (MIDCAB) graft is a surgical technique that is becoming more widely accepted. Through a collaborative effort--interhospital and intrahospital--surgical team members at two hospitals in Kentucky made significant improvements on the MIDCAB procedure that positively influenced patient outcomes (e.g., less time in intensive care, shorter hospital stays, fewer complication, cost savings to the patients and institutions). This article reviews those collaborative efforts and outcomes.