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.

yote Alkaloids: Identification in the Mexican ictus Pelecyphora aselliformis Ehrenberg.

Hordenine, anhalidine, pellotine, 3-demethyltrichocereine, mescaline, dimethoxy-beta-phenethylamine, and the N-monomethyl derivatives of mescaline d 3,4-dimethoxy-beta-phenethylamine have been isolated or identified, or both, in caloid extracts of a Mexican "peyote" cactus, Pelecyphora aselliformis tenberg. This is the first report of the occurrence of some of these alkaloids, including mescaline, in a North American cactus other than Lophophora.

Pharmacokinetics of carbamazepine in normal man.

The bioavailability of commercial carbamazepine talbets with and without meals was compared to a propylene glycol solution respect to extent of absorption in 6 normal humans after a dose of 6 MG/KG. The presence of dose-dependent kinetics within a clinically sigificant range was also investigated. Serum and urine samples were assayed by gal-liquid chromatography (GLC). Carbamazepine is rapidly absorbed from the propylene glycol solution. Eight per cent of the dose was absorbed from the commercial tablet, resulting in therapeutic serum concentrations(30 to 6 mcg/ni). The data were consitent with disolution rate-limited absorption. Mean half-lives ranged from 31 to 35 hr. No dose-dependent kinetics were observed following administration of does of 3. 6. or 9 mg/kg. The fraction of dose abosrbed, the fraction excredted unchanged in urine, the time of maxium serum concentration, and absorption and elimination half-lives appear to be independent of dose. The time course of side effects could not be correlated with serum carbamazepine levels, suggesting that metabolities contributed to side effects.

Identification of structural requirements for analogues of atrial natriuretic peptide (ANP) to discriminate between ANP receptor subtypes.

The structure-activity relationships for affinity and selective binding of atrial natriuretic peptide (ANP) and analogues to guanylate cyclase coupled (CC) and non-cyclase coupled (NC) receptors in rabbit lung membranes are described. We have designed a series of peptides to try to identify the minimal sequence involved in specific recognition of each receptor subtype. The affinity of the peptides was determined from competitive binding experiments. Several peptides derived from the rat ANP sequence, e.g., des-[Phe106, Gly107, Ala115, Gln116]ANP-(103-125)NH2 (4), des-[Cys105,121]ANP-(104-126) (5), and [Acm-Cys105]ANP-(105-114)NH2 (9) have high affinity and selectivity for the noncoupled site. Peptide 4 was the most selective ligand with an affinity superior to that of ANP-(103-126). This compound does not displace the radiolabeled ligand from the guanylate cyclase coupled receptor at the highest concentration tested (100 nM). The structure-activity relationship for affinity and selectivity is discussed. Comparison of the peptide sequences suggests that the structural feature responsible for recognition of the NC site resides in a single sequence of seven contiguous amino acids from the cyclic core of the hormone. The corresponding heptapeptide retains affinity to the guanylate cyclase uncoupled binding site and is proposed to encompass the minimal sequence for specific recognition of the non-guanylate cyclase coupled ANP receptor.

Structure-activity relationships for the carboxy-terminus truncated analogues of angiotension II, a new class of angiotensin II antagonists.

A series of analogues of the recently reported angiotensin II (AII) antagonist [Sar1]AII-(1-7)-amide or des-Phe8[Sar1]AII (3) have been prepared by solid-phase synthesis and purified by reverse-phase liquid chromatography. The agonist and antagonist properties of these carboxy-truncated analogues of AII were determined in the isolated rabbit aorta assay. In the analogues tested, replacement of aspartic acid in position 1 by sarcosine was found necessary to produce significant antagonist activity. At position 7 of the des-Phe8 analogues, prolinamide could be replaced by proline without significant change in the biological activity. However, substitution of 7-prolinamide by either glycinamide or sarcosinamide provided inactive peptides. Methylation of the 4-tyrosine in [Sar1]AII-(1-7)-NH2 preserved the antagonist potency in isolated rabbit aorta. Deletion of the proline at position 7 resulted in inactive hexapeptides, both in the Asp1 and Sar1 series. However synthesis of the N,N-dimethyl amide at the N-terminus afforded hexapeptide [Sar1]AII-(1-6)-N(CH3)2 (10) with a pA2 value of 7.05. All the antagonistic peptides synthesized were fully reversible, competitive antagonists in vitro. These findings indicate that the structural requirements for receptor blockade by these C-truncated analogues are quite stringent with respect to the nature of the amino acid at positions 1 and 6/7. The analogues 2, 3, 7, 10, 11 (saralasin), and 12 (sarmesin) were tested in vivo in the anesthetized rat and were found to inhibit the AII pressor response. In addition, 3 inhibited angiotensin II stimulated aldosterone release from isolated rat adrenal zona glomerulosa cells and had no agonist activity by itself at the doses tested. Interestingly, analogue 3, when injected intracerebroventricularly in conscious rats, failed to antagonize the dipsogenic response to an angiotensin II icv injection and this reflects some heterogeneity in the AII receptor population. Peptide 3 is the first example of an antagonist that discriminates between peripheral and brain receptor subtypes.

First person account: finding myself and loving it.

The article that follows is part of the Schizophrenia Bulletin's ongoing First Person Accounts series. We hope that mental health professionals--the Bulletin's primary audience--will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex-patients, or family members. Our major editorial requirement is that such contributions be clearly written and organized and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients, with experiences they believe should be shared, might encourage these patients to submit their articles to First Person Accounts, Center for Studies of Schizophrenia, NIMH, 5600 Fishers Lane, Rm. 10C-18, Rockville, MD 20857.

Simultaneous analysis of phenobarbital and p-hydroxyphenobarbital in biological fluids by GLC-chemical-ionization mass spectrometry.

A sensitive and specific GLC-chemical-ionization mass spectrometric method was developed for the simultaneous assay of phenobarbital (I) and p-hydroxyphenobarbital (II) in biological fluids (urine and plasma) using stable isotope analogs of the compounds as internal standards. After extraction, the compounds were methylated with diazomethane and quantitated by GLC-chemical-ionization mass spectrometry. The detection limit of the method was 0.1 micrograms/ml for both compounds. The intraday precision (RSD) for 0.4-2.4 micrograms/ml was < 2% for I and < 4% for II. The interday precision for 0.55 and 2.11 micrograms/ml of each compound was 5.5 and 2.9% for I and 7.3 and 5.0% for II, respectively. This method has been applied in several pharmacokinetic studies.

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.

Recurrent acute primary hyperparathyroidism in an adult male patient.

OBJECTIVE: To report the occurrence of recurrent acute primary hyperparathyroidism (HPT), a rare disorder that occurs in only 1 to 2% of patients with primary HPT. METHODS: We describe a patient who had two separate episodes of acute primary HPT and discuss the appropriate treatment of parathyroid crisis. RESULTS: In 1990, primary HPT developed in a 41-year-old man, who underwent surgical removal of a parathyroid adenoma. He remained normocalcemic until 1995, when acute primary HPT developed after lithium therapy was initiated because of depression. Calcium and parathyroid hormone (PTH) levels declined after lithium therapy was discontinued, but they remained slightly above the normal range. Nine months later, he was rehospitalized with acute primary HPT. After stabilization, a second parathyroid adenoma was successfully resected, and calcium and PTH levels subsequently remained normal. In this disorder, levels of PTH are increased up to 20 times normal, and the clinical manifestations are similar to parathyroid carcinoma. Treatment involves rehydration, antiresorptive agents, and parathyroidectomy. Our patient initially was thought to have lithium-induced primary HPT, which can occur in up to 10% of patients on long-term lithium therapy. The mechanism is unknown but may be an alteration of the calcium-PTH "set-point." CONCLUSION: Patients with asymptomatic primary HPT should have close follow-up because of the risk of development of acute primary HPT. Patients at risk, such as those with immobilization or severe illness, should be identified. Drugs known to interfere with calcium metabolism (for example, lithium) should be avoided in patients with primary HPT.

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.

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.

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.

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.

Near-drowning.

Near-drowning is defined as survival for at least some period of time after suffocation from submersion in a liquid. This article is a comprehensive review of the demography, pathophysiology, treatment, and prevention of near-drowning, an accident that affects approximately 6,000 to 7,000 Americans per year. Forty percent of these victims are children younger than 5 years. Alcohol plays a role in approximately one-half of near-drownings of older victims. Major factors prolonging survival are an age of less than 2 years and immersion in cold water (less than 20 degrees C). Hypoxia and acidosis are the primary physiological derangements, and treatment must be directed toward their correction. The hypothermic patient requires special considerations. The role of aggressive cerebral resuscitation has not been elucidated. Prevention of the circumstances that lead to near-drowning must be stressed as a public service.

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.