Sigmoid colon rupture secondary to Credé's method in a patient with spinal cord injury.

Credé's method is a manual suprapubic pressure exerted with a clenched fist or fingers, used to initiate micturition, in patients with spinal cord injury (SCI) who have neurovesical dysfunction. It is usually a benign maneuver unassociated with any major complications. This paper will illustrate a case report involving a sigmoid colon rupture secondary to Credé's method in a patient with SCI. Various techniques of Credé's method are briefly described. It is recommended that patients with quadriplegia avoid forceful use of Credé's method, as it may cause contusion of the abdominal wall and injuries to internal viscera, possibly leading to colonic rupture. It is believed that this is the first reported case of such an unusual complication of Credé's method in patients with SCI.

Surgical aspects of autonomic dysreflexia.

Autonomic dysreflexia (AD) is a characteristic syndrome that occurs in spinal cord injury (SCI) patients with lesions above the sympathetic outflow at T6 and rarely in those with lesions below T10. Symptoms are initiated by noxious stimuli below the level of injury which result in massive sympathetic discharges from the isolated cord. These produce what may be called a sympathetic storm manifest by severe life threatening hypertension. Anesthesiologists and surgeons dealing with SCI patients must know how to recognize this syndrome, how to prevent its occurrence and how to manage it aggressively. Choice of anesthesia is frequently difficult and, in particular, it may be difficult to decide which type of anesthesia is best for patients susceptible to the syndrome. Therefore, we have conducted a retrospective study of SCI patients in the Department of Veterans Affairs Medical Center, Long Beach, California, where the Spinal Cord Injury Service is one of the largest in the country.

Fibrinolytic and protease inhibitory systems in spinal cord injured patients with end-stage renal disease.

Earlier studies have revealed a variety of coagulation abnormalities in patients with long-standing spinal cord injury (SCI) and end-stage renal disease (ESRD). The present study was undertaken to examine the fibrinolytic and protease inhibitory systems in this population. Twelve spinal cord injured men with ESRD were studied. All patients had chronic active urinary tract infections, pressure ulcers and were practically bed-bound. The results were compared with those obtained in a group of 32 normal volunteers. Plasma plasminogen and unstimulated tissue-type plasminogen activator (t-PA) concentrations in the SCI-ESRD group were comparable with those found in the control group. No significant difference was found in plasma plasminogen activator inhibitor (PAI) activity in the two groups. In contrast, plasma alpha 2-antiplasmin antigen concentration and antiplasmin activity were significantly reduced in the study population. In addition, plasma alpha 1-antitrypsin activity and antigen concentration were significantly increased while the alpha 2-macroglobulin activity-to-antigen concentration ratio was significantly reduced in the SCI-ESRD group. Although the mechanism of the observed reduction in alpha 2-antiplasmin and total antiplasmin activity is uncertain, its presence could enhance fibrinolysis in this otherwise thrombosis-prone population. Likewise, elevated alpha 1-antitrypsin could attenuate tissue damage by leukocyte-derived proteases in the face of persistent suppurative infections. The reduced alpha 2-macroglobulin activity-to-antigen concentration ratio was thought to reflect the presence of alpha 2-macroglobulin complexes with various proteases generated by the activation of leukocytes, coagulation, fibrinolytic and other proteolytic systems.

Erythropoietin profile in spinal cord injured patients.

Patients with spinal cord injury (SCI) have a high incidence of anemia. Intact erythropoietin (EPO) production is essential to the maintenance of erythrocyte mass and prevention and correction of anemia. However, the effect of chronic SCI on EPO production remains unclear. We measured plasma EPO concentration in 83 men with longstanding SCI and a group of normal able-bodied individuals. The SCI patients showed a significant reduction in hematocrit, a high prevalence of anemia, and an increased plasma EPO concentration. Active smokers showed a significantly higher hematocrit and lower EPO concentration than nonsmokers. No significant difference was found in hematocrit or EPO between individuals with paraplegia and those with quadriplegia. A negative correlation was found between EPO and hematocrit in SCI patients lacking significant lung disease. Thus, in the absence of renal insufficiency, EPO response to anemia is qualitatively preserved in SCI patients and is largely independent of the level of injury.

Decreased systemic clearance of lorazepam in humans with spinal cord injury.

Serum concentration-time course profiles, serum protein binding, and disposition parameters of lorazepam (LRZ), a benzodiazepine with sedative-hypnotic, anxiolytic, and anti-seizure properties, were studied as part of a systematic effort to define population-specific pharmacokinetic behavior in humans with chronic spinal cord injury (SCI). Twenty-four healthy subjects (nine tetraplegic, six paraplegic, nine able-bodied) were given an IV bolus of 2.0 mg of LRZ. Noncompartmental estimation of pharmacokinetic parameters disclosed a 37% decrease in the total systemic clearance (CL) of LRZ in tetraplegic patients. Altered LRZ clearance was observed independently of significant changes in volume of distribution or serum protein binding. The early elimination of LRZ (0-10 hr) was characterized by wide fluctuations in serum concentration suggestive of impaired enterohepatic circulation and could be distinguished from LRZ elimination observed in able-bodied subjects. We conclude that decreased systemic CL and the altered terminal elimination profile of LRZ are attributable to the pathophysiology of SCI.

Pharmacokinetics of amikacin in serum and in tissue contiguous with pressure sores in humans with spinal cord injury.

Pressure sores are a common occurrence in immobilized patients. They increase morbidity and mortality and impede rehabilitation. Antibiotics are routinely used to assist in effecting a cure when infection is present. Nevertheless, for patients with spinal cord injuries (SCI), strategies for effective therapy with antibiotics based on measurement of concentrations in tissue and pharmacokinetic behavior in extravascular spaces do not exist. By analyzing the concentration-time profile and protein binding of amikacin in the interstitial fluid (IF) in contact with pressure sores, we found that the disposition of amikacin in the tissue contiguous with pressure sores appears to be governed by simultaneous first-order and capacity-limited pharmacokinetic behavior. Amikacin disposition in IF proceeded without a simple relationship to amikacin concentrations in serum, and the time course in IF was not accurately simulated by linear models of amikacin pharmacokinetic behavior. Total amikacin clearance estimated from a pharmacokinetic model using simultaneous first-order and nonlinear intercompartmental transfer of amikacin was not significantly different from clearance calculated by us in a prior study of amikacin pharmacokinetic behavior in patients with SCI. In patients with SCI, optimal use of amikacin in the treatment of infected pressure sores is contingent upon accurate characterization of the pharmacokinetic behavior of this aminoglycoside in serum and in the IF in contact with these lesions. Only methods which quantitate amikacin concentration and protein binding in IF and incorporate a model that can simultaneously simulate nonlinear and linear disposition processes should be relied upon to influence therapeutic decision making.

Amikacin pharmacokinetics in patients with spinal cord injury.

The influence of chronic (greater than 1 yr duration) spinal cord injury (SCI) on the disposition of amikacin was studied in seven healthy subjects with SCI (five paraplegic, two tetraplegic) and seven able-bodied controls (intact neuraxes). The time course of amikacin serum concentration after a 30-minute infusion (7.5 mg/kg) was followed for up to 8.5 hours using fluorescence polarization immunoassay. Pharmacokinetic values were estimated by a noncompartmental analysis (NC). Amikacin steady-state volume of distribution (Vss) was increased to 0.20 +/- 0.04 l/kg (mean +/- SD) as compared to 0.17 +/- 0.02 l/kg in able-bodied controls (p 0.03), and its mean terminal elimination half-life in patients with SCI was prolonged by 0.64 hours over the control value of 2.11 +/- 0.27 hours (p 0.01). The NC estimated mean residence time (MRT) in patients with SCI (3.65 +/- 0.75 hrs) was 0.89 hours longer than that observed in controls (p 0.03). Our data suggest that the Vss, half-life, and MRT of amikacin are increased in persons with chronic SCI. As a result, amikacin dosing regimens developed in able-bodied humans may demonstrate diminished efficacy when extrapolated uncritically to these patients.

Theophylline disposition in tetraplegic man.

We studied the time-course of serum theophylline concentration after a 30-minute intravenous infusion of aminophylline (6 mg/kg) in 18 traumatic tetraplegic (nine smoking, nine nonsmoking) and in six control (nonsmoking) subjects. All study subjects were healthy men with normal renal function. Pharmacokinetic parameters were calculated from a linear regression analysis of the terminal log-linear portion of the log serum theophylline concentration-time curves. The terminal elimination kinetics of theophylline in this study were best characterized by first order elimination from a one compartment-open model. A statistically significant difference (P less than .05) was demonstrated between the means and variances of theophylline clearance (Cl ml/kg/min) and hours of half-life (t1/2) for control subjects and smoking tetraplegics. Total body clearance of theophylline was greater in all tetraplegic subjects, the greatest difference in total clearance of theophylline adjusted to body weight being observed between tetraplegic smokers and nonsmoking controls with an intact central nervous system (P less than .05). Theophylline volume of distribution (Vdarea) did not differ significantly from Vdarea in able-bodied subjects. Tetraplegic individuals have multiple disorders and marked pharmacokinetic variation, which might be expected to make serum concentration and toxicity of theophylline unpredictable using population averages.

The absolute bioavailability of oral theophylline in patients with spinal cord injury.

The absolute bioavailability of oral theophylline in five tetraplegic, five paraplegic and three control (intact neuraxes) subjects was studied. All were healthy nonobese males between 20 and 60 years of age, with normal renal and hepatic function. More than 1 year had elapsed from the date of injury in all of the patients with spinal cord injury. None of the study subjects was taking medications known to interfere with theophylline metabolism or the analytic methodology. Each received theophylline in an equivalent amount orally, and by intravenous infusion on 2 occasions separated by not less than 2 weeks. The time course of serum theophylline concentration was followed for up to 24 hours and the area under each oral and intravenous curve extrapolated to infinity (AUC male infinity) was compared using a linear, least-squares, best-fit BASIC program (ESTRIP). A statistically significant difference between means and variances of the absolute bioavailability of oral theophylline, AUCoral male infinity/AUCIV male infinity, (AUCratio +/- SD) was demonstrated in the tetraplegic subjects who showed decreased bioavailability (AUCratio = 0.67 +/- 0.04, range 0.63-0.73) as compared to the paraplegic (AUCratio = 0.95 +/- 0.09, range 0.84-1.08) and control subjects (AUCratio = 0.90 +/- 0.12, range 0.78-1.02). A decrease in the bioavailability of oral theophylline in tetraplegic subjects has not previously been described and may be caused by impaired gastric emptying, which frequently characterizes high myelopathy. Diminished bioavailability could result in underestimation of loading and maintenance doses in tetraplegic humans.

The role of hyperbaric oxygen in the management of Fournier's gangrene.

Fournier's gangrene of the external genitals is a complex entity characterized by acute onset, rapid progress to gangrene, toxemia and high mortality rate. The disease may be primary as described by Fournier or secondary with a detectable cause in the colo-rectal area, the lower urogenital tract or in the perineum. The disease may affect healthy young males (originally described by Fournier) or elderly subjects especially with general ill health, cancer, diabetes, liver or renal failure, immunosuppression, etc. The microbiology is as complex as the etiology. The nosiology is likewise complex. Because the mortality is high, it is important to be aggressive in therapy. Triple attack is necessary, viz.: antibiotic coverage for aerobes and anaerobes, general supportive measures and adequate surgical debridement. We, recommend Hyperbaric Oxygen Therapy (HBO) treatment in specialized centers as an adjunctive measure since we had no mortality in the cases we treated. In expert centers, HBO has very few complications which are outweighed by the benefit the patient gets. The one-man chamber is the commonest in use, but for a compromised patient the multiplace may be more appropriate. In the very early stage, HBO may avert gangrene or reduce it. It is important to have a high index of awareness of this disease amongst the medical profession. More work is needed for the more precise definition, classification and management of the complex syndrome of Fournier.

The acute abdomen in spinal cord injury patients.

After return of the reflex arc below the level of anaesthesia, the spinal cord injury (SCI) patient will manifest an intra-abdominal emergency by the clinical signs of dysreflexia depending upon the level and completeness of the cord lesion. Thirty-six SCI patients are presented to correlate the autonomic response to visceral disease with the level of their cord lesion demonstrating that early recognition and diagnosis is possible in these patients.

Gentamicin disposition kinetics in humans with spinal cord injury.

The disposition kinetics of gentamicin, an aminoglycoside antibiotic, were studied in seven tetraplegic and six paraplegic volunteers. The volume of distribution of gentamicin in l/kg of body weight varied in a statistically significant way from values of this parameter measured in normal subjects. The elimination of gentamicin in spinal man proceeded in a log-linear fashion accurately characterized by a one compartment open-model with a half-life of approximately 2 hours. The clinical significance of altered disposition kinetics and an increased intersubject variability in gentamicin disposition in spinal man as compared to normal subjects is unknown. The existence of these observed differences in pharmacokinetic parameters, however, emphasizes the need to define individual pharmacokinetic profiles and individualize dosing regimens in spinal man. The data presented are supportive of the hypothesis that spinal man constitutes a discreet therapeutic population.