Critical illness myopathy unrelated to corticosteroids or neuromuscular blocking agents

Acute myopathy occurs in critically ill patients, receiving neuromuscular blocking agents or corticosteroids during intensive care hospitalisation. We report three patients with acute quadriplegic myopathy, two of whom were not exposed to corticosteroids or neuromuscular blocking agents. The first of these latter two patients had a history of generalised anoxia with coma related to surgery, complicated by multiple organ failure and sepsis. The second patient, suffering from acute leukaemia, developed sepsis and acute respiratory distress syndrome with the need for mechanical ventilation in the intensive care unit. Electrophysiological studies and muscle biopsy findings were consistent with the diagnosis of critical illness myopathy with loss of myosin filaments. Selective loss of myosin was confirmed by biochemical analysis of muscle. These findings demonstrate that acute myopathy with loss of myosin filaments may occur in patients with severe systemic illness without exposure to corticosteroids or neuromuscular blocking agents.     

Acute myopathy associated with combined use of corticosteroids and neuromuscular blocking agents

OBJECTIVE: To review the occurrence and pathophysiology of myopathy associated with combined use of neuromuscular blocking agents (NMBAs) and systemic corticosteroids. DATA SOURCES: A MEDLINE search (1985 to July 1995, English language) yielded case reports and clinical studies involving myopathy or weakness associated with the use of NMBAs and/or corticosteroids. References cited in those articles were reviewed. DATA SYNTHESIS: Prolonged muscle weakness has been reported in intubated patients in the intensive care unit (ICU) who were receiving NMBAs and/or corticosteroids. Many cases involved the use of both agents in individuals with no underlying risk factors. The term "blocking agent-corticosteroid myopathy" (BACM) has been used to describe this myopathy when it develops following combined use of these agents. Features common to BACM include prolonged weakness, elevated creatine kinase concentrations, myopathic features on electromyography, normal nerve conduction and sensation, and reduced deep tendon reflexes. Muscle biopsy results vary, but tend to show type 1 and/or 2 fiber atrophy without inflammation. Some recently reported cases revealed thick myosin myofilament loss, which is consistent with findings in denervated rat muscle after exposure to corticosteroids. Two small prospective studies reported that 36-50% of mechanically ventilated patients receiving either one or both drugs developed prolonged weakness. CONCLUSIONS: NMBAs and corticosteroids alone have both been reported to cause myopathy in patients in the ICU. When coadministered, these agents appear to confer an even greater risk of myopathy; the exact pathology is not understood. Concomitant use of NMBAs and corticosteroids should be avoided if possible. Guidelines for cautious use and careful monitoring are suggested when combined use is deemed necessary.     

Approaches to short-acting neuromuscular blocking agents: nonsymmetrical bis-tetrahydroisoquinolinium mono- and diesters

Nonsymmetrical bisquaternary mono- and diesters combining the potency-enhancing properties of the (1R)-laudanosinium group with a second unhindered quaternary ammonium moiety have been studied as a means of promoting short action with high-potency neuromuscular block. Atracurium-related nonsymmetrical diesters showed high potency, freedom from vagal blockade at neuromuscular blocking doses, and short action. Nonsymmetrical monoesters were short acting but showed varying degrees of vagal block.     

Effects of neuromuscular blocking agents on excitatory transmission and gamma-aminobutyric acidA-mediated inhibition in the rat hippocampal slice

BACKGROUND: Although neuromuscular blocking agents do not cross the blood-brain barrier, they may penetrate the central nervous system under particular circumstances and eventually cause neurotoxic consequences. METHODS: The effects of neuromuscular blocking agents on excitatory and inhibitory transmission in area CA1 of rat hippocampal slices were investigated using extracellular and intracellular recording techniques. RESULTS: Application of atracurium in the perfusion medium resulted in a dose-dependent enhancement of excitatory synaptic responses averaging 48.7 +/- 4.3% at a concentration of 10 nM. This effect was correlated with an increase in the size of the presynaptic fiber volley. Laudanosine, but not pancuronium bromide or vecuronium bromide, produced similar changes. In addition, atracurium and laudanosine blocked inhibitory transmission and reduced intracellularly recorded gamma-aminobutyric acidA receptor-mediated potentials. These effects were observed only at concentrations >1 microM and were not reproduced by pancuronium bromide and vecuronium bromide. CONCLUSIONS: Atracurium and its metabolite, laudanosine, contrary to pancuronium bromide and vecuronium bromide, produce two distinct effects on hippocampal slices. They enhance excitatory transmission and neuronal excitability and they block inhibitory gamma-aminobutyric acidA-mediated synaptic responses.     

Ansa-recurrent nerve anastomosis for vocal cord paralysis due to mediastinal lesions

Recurrent laryngeal or vagus nerve injuries in the mediastinum are repaired rarely because of technical difficulties. Impairment in phonation is especially severe in patients with respiratory dysfunction. We performed a simple and less invasive reconstruction, ansa cervicalis-recurrent laryngeal nerve anastomosis in the neck, to improve phonation in 2 patients. Although the reinnervated vocal cord did not regain normal movement, both of the patients obtained excellent improvement in phonation.     

Peripheral neuropathy and neuromuscular blockade presenting as prolonged respiratory paralysis following critical illness

We report two patients who following critical illness presented with generalised paralysis associated with persistent failure to breathe. Both patients eventually recovered and were weaned from the ventilator. The cause of the paralysis was an unusual peripheral neuropathy in the first patient and persistent neuromuscular blockade secondary to vecuronium in the second. It is important to consider a reversible, possibly even iatrogenic, cause of this type of complication.     

Comparative recovery from three nondepolarizing neuromuscular blockers in a patient before and after chronic anticonvulsant therapy: a case report

We describe a 51-year-old patient undergoing a second neurosurgical procedure after being prescribed anticonvulsant therapy. The patient had significant changes in the duration of action of identical doses of nondepolarizing muscle relaxants and we were able to compare the duration of action of neuromuscular blockers before and after the chronic administration of anticonvulsant therapy. A brief review of the possible mechanisms of action of the acceleration of the patient's recovery profile is also presented.     

Sj?gren's syndrome presenting as hypokalemic paralysis due to distal renal tubular acidosis

A 57-year-old woman presented with a flaccid paralysis, muscle tenderness, and respiratory depression. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis and abnormally acidified urine. The urinary anion gap was positive in the presence of acidemia, thus establishing the diagnosis of distal renal tubular acidosis (DRTA). The patient fully recovered after potassium and alkali replacement. Further investigation revealed Sj?gren's syndrome as the underlying cause of DRTA.     

Adjuncts to analgesia. Sedation and neuromuscular blockade

This article provides an overview of some of the current issues involved in sedation and anxiolysis in the intensive care unit. The problems involved in trying to monitor sedation levels are discussed, as are some of the newer options available for physiologic monitoring of the central nervous system. The problem of abnormal mental states in the intensive care unit and the range of antidepressant therapy now available are also covered. The importance of sleep deprivation and the properties of the neuromuscular blockers are also discussed.     

Prolonged fever due to Mycobacterium avium complex (MAC) disease in advanced HIV infection: a public health concern

From March 1997 to June 1998, infectious etiologies of prolonged fever was prospectively investigated in 104 advanced human immunodeficiency virus (HIV) infected patients admitted to Siriraj Hospital. The etiology could be identified in 91 cases (87.5%). Of these, blood cultures from 68 patients yielded mycobacteria and fungi. Mycobacterium avium complex was the most common blood isolate in 24 per cent of the patients; followed by Mycobacterium tuberculosis in 20.2 per cent, Cryptococcus neoformans in 5.8 per cent, Penicillium marneffei in 5.8 per cent. During the course of febrile illness, 79 of the 91 patients (86.8%) exhibited focal lesions. Weight loss, elevated serum alkaline phosphatase were often found to be significantly more associated with MAC bacteremia (P < 0.05). Pulmonary involvement significantly correlated more with M. tuberculosis bacteremia than MAC bacteremia (P < 0.05). No cause could be identified in 13 cases. Mycobacterium blood culture alone established the etiologies in 68 cases (65.4%). Of the 25 patients with disseminated MAC (DMAC) infection, nine patients died during hospitalization. Another three cases died within a few months of appropriate anti-MAC chemotherapy. We concluded that the risk of DMAC infection in advanced AIDS patients in Thailand is high when low CD4 lymphocyte count is established. The prolonged fever resulted from DMAC in advanced HIV infection is warrant to be public health concern. Mycobacterium blood culture is a most valuable tool contributing to the diagnosis of infectious agents in this condition. The guidelines of 1997 USPHS/IDSA should be followed to give chemoprophylaxis against DMAC disease in patients with advanced HIV infection and a CD4 count less than 50 cells/mm3.     

Reactivity and aggression in the rat: Induction by !a-adrenergic blocking agents injected ventral to anterior septum but not into lateral septum.

Intracranial injections were made bilaterally through permanently implanted cannulas ending in the lateral septum or in the region ventral to the anterior septum of 78 male hooded rats. Ss were first screened with injections of a local anesthetic, lidocaine, which blocks both synaptic and axonal conduction. Those Ss that showed an increase in reactivity and aggression were then injected with a synaptic transmitter blocking agent. Results show that transmitter blocking agents reproduced the effect of the local anesthetic only in the region ventral to the anterior septum and that α-adrenergic (phentolamine, tolazoline), but not β-adrenergic (propranolol, hydralazine), cholinergic (atropine, hyocine), or dopaminergic (haloperidol) blocking agents were effective. Results suggest that synapses in the forebrain system controlling reactivity and aggression are α-adrenergic and are located in the region ventral to the anterior septum just lateral to the diagonal band of Broca. The septum itself may be involved only to the extent that it is transversed by fibers of passage. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The action of blocking agents applied to the inner face of Ca(2+)-activated K+ channels from human erythrocytes

The 'capacity' of the vagina and the compliance of the vaginal wall was measured in bilaterally ovariectomized ewes (n = 7) before and after treatment with exogenous oestradiol and progesterone; in nulliparous ewes (n = 7) at oestrus (Day 0) and dioestrus (Day 10) and during pregnancy, and in another group of pregnant ewes (n = 15) treated with exogenous oestradiol and progesterone. Measurements were remarkably consistent within individual animals but there were considerable differences between individual animals. The 'vaginal capacity' and the compliance of the vaginal wall were greater at oestrus than during dioestrus. In the same seven ewes, which were studied during their first and second pregnancies, the 'capacity' of the vagina increased whereas the compliance of the vaginal wall declined; from 90 days to term both parameters remained fairly constant. For the first 2 months of gestation the vaginal capacity was greater in year 2 than year 1 but this was reversed during the last 3 months. The compliance of the vaginal wall was significantly greater (P < 0.0001) in year 2 than year 1 at all stages of pregnancy. In ovariectomized ewes, progesterone only significantly increased the vaginal capacity at the highest dose rate (viz. 100 mg); the compliance of the wall was reduced at the 25 and 50 mg dose rates. Oestradiol produced an inconsistent dose response effect; whilst 5 mg and 20 mg had no effect upon the vaginal capacity, the 10 mg dose rate significantly reduced it. Similarly, the highest and lowest dose rates reduced the compliance of the vaginal wall but the 10 mg dose rate increased it. At 90 and 120 days of gestation, both 5 mg oestradiol and 100 mg progesterone increased the vaginal capacity but reduced the compliance.     

Low-titer cold-hemagglutinin disease. Mechanism of hemolysis and response to corticosteroids

We studied two patients with a low-titer cold-hemagglutinin disease syndrome to investigate the mechanism of hemolysis and the therapeutic response to corticosteroids. The antierythrocyte antibody was of the IgM class, had a high thermal amplitude and had enough activity of 37 degrees C to account for the hemolysis. The capacity of peripheral blood monocytes to increase the osmotic fragility of C3-coated erythrocytes suggests that macrophage interaction with C3-coated erythrocytes explains the observed in vivo spherocytosis. Both patients responded to high-dose corticosteroids. The data suggest that the steroid effect is probably due to alteration of macrophage complement-receptor function. These studies demonstrate the importance of antibody activity at body temperature in producing hemolysis, particularly in this variant of cold-hemagglutinin disease. The response to steroids suggests the efficacy of corticosteroid therapy in alleviating hemolysis due to macrophage recognition of erythrocytes coated with IgM and C3.