Margaret R. Weglinski

Malignant Hyperthermia Testing in Patients with Persistently Increased Serum Creatine Kinase Levels

We describe 49 neurologically asymptomatic patients with persistently increased serum creatine kinase (CK) levels (idiopathic hyperCKemia or IHCK) who were referred to our institution for diagnostic muscle biopsy, including malignant hyperthermia (MH) susceptibility testing between 1979 and 1993.Muscle biopsy samples of the vastus lateralis were obtained for histologic analysis and MH contracture testing with halothane and caffeine. From 1979 to November 1987, patients were tested for MH in accordance with a standardized institutional protocol. After November 1987, contracture testing was performed according to the recently adopted North American MH Group protocol. In both protocols, a patient was considered to be MH susceptible (MHS) if one or more muscle strip demonstrated an abnormal contracture response after exposure to 3% halothane, 2% halothane, or caffeine alone. Twenty-four of the 49 IHCK patients (49%) had positive contracture tests. No significant correlation was found between the magnitude of CK increase and the incidence of MHS or histologic abnormalities. Unexplained persistently increased CK levels in an otherwise healthy patient should alert the anesthesiologist to the possibility of MHS and/or myopathy. (Anesth Analg 1997;84:1038-41)

Correlation of regional cerebral blood flow with ischemic electroencephalographic changes during sevoflurane-nitrous oxide anesthesia for carotid endarterectomy.

Background Carotid endarterectomy necessitates temporary unilateral carotid artery occlusion. Critical regional cerebral blood flow (rCBF) has been defined as the rCBF below which electroencephalographic (EEG) changes of ischemia occur. This study determined the rCBF50, the rCBF value at which 50% of patients will not demonstrate EEG evidence of cerebral ischemia with carotid cross‐clamping. Methods Fifty‐two patients undergoing elective carotid end‐arterectomy were administered 0.6–1.2% (0.3–0.6 minimum alveolar concentration) sevoflurane in 50% nitrous oxide (N2 O). A 16‐channel EEG was used for monitoring. The washout curves from intracarotid133 Xenon injections were used to calculate rCBF before and at the time of carotid occlusion by the half‐time (t1/2) technique. The quality of the EEG with respect to ischemia detection was assessed by an experienced electroencephalographer. Results Ischemic EEG changes developed in 5 of 52 patients within 3 min of carotid occlusion at rCBFs of 7, 8, 11, 11, and 13 ml [center dot] 100 g sup ‐1 [center dot] min sup ‐1. Logistic regression analysis was used to calculate an rCBF50 of 11.5 +/‐ 1.4 ml [center dot] 100 g sup ‐1 [center dot] min sup ‐1 for sevoflurane. The EEG signal demonstrated the necessary amplitude, frequency, and stability for the accurate detection of cerebral ischemia in all patients within the range of 0.6–1.2% sevoflurane in 50% N2 O. Conclusions The rCBF50 of 0.6–1.2% sevoflurane in 50% N2 O, as determined using logistic regression analysis, is 11.5 +/‐ 1.4 ml [center dot] 100 g sup ‐1 [center dot] min sup ‐1. Further, in patients anesthetized in this manner, ischemic EEG changes due to carotid occlusion were accurately and rapidly detected.

Transient global amnesia after general anesthesia.

Transient global amnesia (TGA) is an amnestic syndrome, clinically dramatic but benign in nature. The hallmark of TGA is brief inability to form new memories and recall past memories despite otherwise normal neurological function. In a significant number of patients with TGA a stressful precipitating factor can be identified. We report two cases of TGA after uneventful general anesthesia. Anesthesia per se does not appear to be a direct trigger of TGA, as our first patient had a second anesthetic the next day without recurrence of TGA. Because the presentation of TGA can be dramatic and may mimic an acute cerebral ischemic event, a thorough neurologic evaluation should be pursued.

The Effects of Transient Hyperglycemia on Brain Glucose in Rats Anesthetized with Halothane

The effects of transient hyperglycemia on brain glucose and the relationship between blood and brain glucose were studied in 76 Sprague-Dawley rats anesthetized with halothane 1% inspired. In a common control group, blood and brain glucose were determined prior to any intervention (n = 10). A second group of 30 rats was given an iv infusion of 3.9 ml of saline over a 30-min period, and blood and brain glucose were subsequently determined at several time points: 30 min (immediately after the saline infusion), 45, 60, 90, or 120 min (n = 6 for each time point). A third group of 36 rats was administered 3 g/kg of glucose in 3.9 ml of iv saline over a similar 30-min period, and blood and brain glucose were measured at the same time periods as in saline-treated rats and also when half of the glucose infusion was given (time = 15 min; n = 6 for each time point). In the common control group, blood glucose was 114 +/- 14 mg/dl (6.4 +/- 0.8 mumol/ml; mean +/- SD) and brain glucose was 2.41 +/- 0.59 mumol/g. Saline infusion had no effect on brain or blood glucose. In contrast, glucose infusion in the study group produced significant increases in both blood and brain glucose, achieving maximal values of 488 +/- 60 mg/dl (27.4 +/- 3.4 mumol/ml) and 7.62 +/- 0.52 mumol/g, respectively, at the 30-min measurement period. The ratio of brain to blood glucose, normalized so that the common control group data achieved a value of 1, was less than unity during the period of glucose infusion. This ratio reached a nadir of 0.75 +/- 0.07 at the 30-min measurement period (P less than 0.05 versus saline infusion). Thereafter, with the cessation of glucose infusion, the ratio returned to 1 and eventually exceeded unity: the peak ratios were 1.23 +/- 0.13 and 1.16 +/- 0.21 at the 60- and 90-min period, respectively (P less than 0.05 versus saline treatment). The authors concluded that during periods of rapidly fluctuating blood glucose, there is a hysteresis between blood and brain glucose values; hence, it may not be possible to accurately estimate brain glucose by measuring blood glucose.

New-Onset Neurologic Deficits After General Anesthesia for MRI

Two patients with spine disease were unable to tolerate supine placement for magnetic resonance imaging (MRI) because of severe back pain. General anesthesia was administered to enable the patients to undergo MRI. Both patients awakened from anesthesia with new-onset paraplegia and underwent emergency decompressive laminectomy. Acute paraplegia after anesthesia occurs infrequently and is most commonly associated with mechanical injury, vascular compromise, or anesthetic technique. The physical limitations of the MRI environment make it difficult to position some patients in a manner that accommodates their pathophysiology and may place certain patients at risk of neurologic compromise. For this subset of patients, the necessity of MRI with general anesthesia should be reassessed and alternative imaging methods considered.

Exome analysis identifies Brody myopathy in a family diagnosed with malignant hyperthermia susceptibility

Whole exome sequencing (WES) was used to determine the primary cause of muscle disorder in a family diagnosed with a mild, undetermined myopathy and malignant hyperthermia (MH) susceptibility (MHS). WES revealed the compound heterozygous mutations, p.Ile235Asn and p.Glu982Lys, in ATP2A1, encoding the sarco(endo)plasmic reticulum Ca2+ ATPase type 1 (SERCA1), a calcium pump, expressed in fast‐twitch muscles. Recessive mutations in ATP2A1 are known to cause Brody myopathy, a rare muscle disorder characterized by exercise‐induced impairment of muscle relaxation and stiffness. Analyses of affected muscles showed the absence of SERCA1, but SERCA2 upregulation in slow and fast myofibers, suggesting a compensatory mechanism that partially restores the diminished Ca2+ transport in Brody myopathy. This compensatory adaptation to the lack of SERCA1 Ca2+ pumping activity within the muscle explains, in part, the mild course of disease in our patient. Diagnosis of MHS in this family was secondary to a loss of SERCA1 due to disease‐associated mutations. Although there are obvious differences in clinical expression and molecular mechanisms between MH and Brody myopathy, a feature common to both conditions is elevated myoplasmic Ca2+ content. Prolonged intracellular Ca2+ elevation is likely to have led to MHS diagnosis in vitro and postoperative MH‐like symptoms in Brody patient.

The effects of continuous glucose infusion on blood, plasma, and brain glucose in anesthetized rats

In models of cerebral ischemia, it is important to rigidly control brain glucose in the peri-ischemic period because alterations in brain glucose can affect the severity of the postischemic injury. The following study evaluated the effect of a continuous glucose infusion as a means of producing stable increases in brain glucose that could be monitored by measuring either blood or plasma glucose. Fifty-four halothane-anesthetized rats were studied. Rats received either no treatment (control group; N = 6), saline 2 ml/h (N = 24), or glucose 1 g/kg per h in saline 2 ml/h (N = 24). In the latter two groups, samples of blood, plasma, and brain glucose were obtained at either 30, 60, 120, or 180 min of the infusion (N = 6 per group per sample period). Saline infusion had no effect on either blood, plasma, or brain glucose. In contrast, glucose infusion produced a significant increase in all three variables, achieving plateau increases during the 60-180 min measurement periods [blood glucose = 197 +/- 20 mg/dl (mean +/- S.D.) at 60 min, 220 +/- 34 mg/dl at 120 min, and 217 +/- 22 mg/dl at 180 min versus control blood glucose = 89 +/- 10 mg/dl]. Regardless of the treatment group, there was excellent correlation between blood and plasma glucose (r = 0.99; P much less than 0.001), blood and brain glucose (r = 0.96; P much less than 0.001), and plasma and brain glucose (r = 0.97; P much less than 0.001). The authors conclude that continuous glucose infusions are an effective method to produce stable increases in brain glucose in experimental models; and, in contrast to other methods for achieving brain glucose increases, the brain glucose increases can be accurately assessed by measuring blood or plasma glucose.