Biomedical subjects
Publications and source records attributed to W H Spivey.
The neurologic complications of cocaine toxicity are responsible for a major portion of the morbidity and mortality associated with cocaine. Most of the complications appear to be related to the hyperadrenergic state induced by cocaine and may be treated symptomatically. Diazepam is the most effective drug for cocaine-induced seizures.
Our clinical observations suggested that vigorous fluid therapy in children often resulted in hypokalemia. A retrospective review was conducted of four years of admissions to a pediatric intensive care unit. A total of 29 patients were identified who received at least 20 ml/kg of intravenous fluid in their first hour of care and had a pretreatment and posthydration serum K obtained. The potassium levels dropped from a mean pretreatment value of 4.6 +/- 1.0 mEq/L to a mean of 3.3 +/- 0.8 mEq/L (P less than 0.005). Coincidental arterial pH measurements were available in 16 cases. A separate analysis of potassium change in this group revealed that pH change alone could not account for the drop in serum K. Significant hypokalemia may occur after aggressive rehydration of critically ill pediatric patients.
Conventional nebulized beta-agonist therapy has met with disappointing results in an increasing number of moderate to severe asthmatics who may be characterized as "poor responders." Thirty-eight patients suffering from acute exacerbations of moderate to severe asthma were treated in an emergency department with an intravenous infusion of saline placebo or 1.2 g of magnesium sulfate after conventional beta-agonist therapy failed to produce significant improvement in peak expiratory flow rate. Nineteen patients were randomized into each of two groups in a placebo-controlled, double-blind clinical trial. The treatment group demonstrated an increase in peak expiratory flow rate from 225 to 297 L/min as compared with 208 to 216 L/min seen in the placebo group. In addition, the number admitted vs discharged was significantly better for the treatment group (7 vs 12) than the placebo group (15 vs 4). Intravenous magnesium sulfate may represent a beneficial adjunct therapy in patients with moderate to severe asthma who show little improvement with beta-agonists.
Recent interest in the intraosseous (IO) route as an alternative venous access for drug and fluid administration has increased. This study examined the physiological and skeletal pathological effects of IO NaHCO3 in pigs. In the pathological studies, swine (8-10 kg) received NaHCO3 (1 mEq/kg) in one tibia and saline (1 ml/kg) in the other tibia via an 18-gauge spinal needle inserted into the anteromedial surface of the bone. The animals were then observed for one month, sacrificed, and the tibias were isolated, sectioned, and stained for pathological examinations. The physiological effects of IO NaHCO3 infusion were studied and compared with that of intravenous (IV) administration using a cardiac arrest model as previously described. The results demonstrated that NaHCO3 had no effect on the mean arterial blood pressure and plasma catecholamine levels, but increased arterial pH values within two minutes of administration. Similar effects were found with IV NaHCO3. Pathological data indicated signs of minimal local increase in skeletal turnover associated with IO NaHCO3 infusion. It is concluded that the IO route is a safe alternative venous access for NaHCO3 administration in swine.
Informed consent serves as the basis for a partnership between patients and physicians as they attempt to find better methods of diagnosis and treatment. Despite the importance of informed consent, this is an area of research that is frequently overlooked. In fact, an improperly designed consent form is the most common reason research protocols are rejected or approval is delayed. The essential elements of informed consent and problems obtaining informed consent from patients is an emergency department are reviewed.
IV magnesium sulfate was administered to a 72-year-old man with acute respiratory failure secondary to a severe asthma attack. The patient had clinically deteriorated despite aggressive standard treatment and evidenced acidosis and hypercarbia by arterial blood gas determination. An IV dose of 1 g MgSO4 produced rapid clinical and arterial blood gas improvement and enabled management of the patient without endotracheal intubation and mechanical ventilation. This is the first reported case of the use of IV MgSO4 to prevent intubation and assisted ventilation in a patient with acute respiratory failure complicating asthma.
The technique of intraosseous infusion has attracted increasing interest in recent years, and has proven valuable for drug administration. This study was undertaken to determine whether it was also a potential route for fluid resuscitation. Thirteen- or eighteen-gauge tibial intraosseous needles were placed in eight "large" (mean weight, 14.4 kg) and eight "small" (mean weight, 5.8 kg) swine and the flow rate of blood and saline measured under gravity and 300 mm Hg. Flow was significantly greater using 13-gauge needles in the "large" swine, significantly greater for saline than for blood, and for pressure infusion versus gravity in all animals. A fluid bolus of 20 ml/kg could be given to all animals in less than 10 minutes using pressure infusion. These data suggest that intraosseous infusion is a reasonable initial step in fluid resuscitation of pediatric subjects until more conventional vascular access has been established.
The reported study determined whether timolol would afford a protective effect by preventing the coronary occlusion-induced arrhythmias associated with the increase in plasma norepinephrine (NE) and epinephrine (E). Ten anesthetized cats received saline or timolol (5 mg/kg, IV) five minutes after coronary occlusion of the left anterior descending coronary artery 10 to 14 mm below its origin. Coronary occlusion produced arrhythmia in three of the cats that received saline and in four of the cats that received timolol. Three of the saline-treated cats died in cardiogenic shock; two were sacrificed six hours postocclusion. Four of the timolol-treated cats died in congestive heart failure postcoronary occlusion. There was a gradual increase in NE (P greater than .05) and E (P less than .05) in both groups after coronary occlusion. Death produced a significant increase in NE and E levels. Timolol did not modify the occurrence of arrhythmias and the associated increase in plasma NE and E that developed after coronary occlusion and at death.
The effect of no drug or timolol (5 mg/kg, PO, for 1, 2, or 8 weeks on postganglionic cardiac sympathetic neural discharge, blood pressure, heart rate and beta-receptor density after acute coronary occlusion of the left anterior descending artery was compared. Beta-receptor density, determined by binding of 3H-dihydroalprenolol, was examined in the myocardium (LA = left atrium, RA = right atrium, LV1 = proximal and LV2 = distal left anterior descending artery distribution, LV3 = posterior left ventricle, S = septum, and RV = right ventricle). In control cats (no coronary occlusion or timolol) beta-receptor density of LV2 and LV3 was greater (P less than .05) than LA, RA, LV1, and RV. LV3 was greater (P less than .05) than S and RA, and LA was less than S. Longer treatment with timolol increased beta-receptor density. When compared with no timolol, beta-receptor density was greater in RA after 8 weeks and in LV1 after 2 weeks and not different in LV2 and S. Beta-receptor density and LV3 and RV were greater after 8 weeks than after 1 week or no timolol. Spearman rank correlation coefficients between dose and beta-receptor density revealed an increase (P less than .05) for all heart areas. Heart rate did not vary before timolol and was decreased after all doses of timolol. Timolol increased the mean times to coronary occlusion-induced death although the increase was not statistically significant. Timolol did not prevent postganglionic cardiac sympathetic neural discharge associated with arrhythmia. Timolol may increase beta-receptor density and decrease synaptic norepinephrine, causing a decreased release per cardiac sympathetic nerve impulse. Alternatively, molecules of timolol may accumulate in nerve endings and be released in greater concentrations at the receptors. This could explain the protection against coronary occlusion-induced arrhythmia and death.
The intraosseous (IO) route provides a rapid and effective alternative venous access in the pediatric population when the conventional intravenous (IV) route cannot be easily obtained. DL-propranolol, a beta-adrenoceptor antagonist, exhibits antiepileptic activity in various animal seizure models. This study assessed the efficacy of IO propranolol in suppressing pentylenetetrazol (PTZ)-induced seizure activity in pigs. Domestic swine (13-20 kg) were prepared for recordings of arterial blood pressure, ECG and electrocortical activity. Seizure activity was induced by pentylenetetrazol (PTZ; 100 mg/kg; IV). Sixty seconds after the onset of seizure activity, the animals either received no drug (control) or propranolol (IV or IO via an 18-gauge spinal needle placed in the right proximal tibia). A transient increase (16.3-50.0%) in the mean arterial blood pressure (MAP) was observed following PTZ administration. Both IO and IV propranolol significantly suppressed the seizure duration (SD) (sec/min interval) at 1 min following drug administration; SD control, 36.3 +/- 4.8; IV propranolol, 12.3 +/- 5.1; IO propranolol, 18.3 +/- 6.0. In addition, both IV and IO propranolol produced a maximal decrease of 32-38% in the basal heart rate; and reduced the transient increase in MAP elicited by PTZ, with no significant effect on the basal MAP. The data demonstrate that 1) propranolol possesses anticonvulsant activity against PTZ-induced seizure in the pig, and 2) the intraosseous route is a rapid and effective alternative venous access for propranolol administration in swine.
The effect of timolol on postganglionic cardiac sympathetic neural discharge, blood pressure, heart rate, and rhythm changes associated with acute coronary occlusion of the left anterior descending artery was examined and compared with the effects of the beta blockers practolol and metoprolol. Timolol (5 mg/kg, IV) was infused 15 minutes prior to coronary occlusion in cats anesthetized with alpha-chloralose. Control heart rate fell from 129 +/- 10 to 106 +/- 2 one minute prior to coronary occlusion and remained at 106 +/- 2 beats/minute in the minute prior to arrhythmia. Control blood pressure fell from 126 +/- 20 to 91 +/- 19 and stabilized at 99 +/- 19 mm Hg one minute prior to coronary occlusion. Mean time to arrhythmia and death was 4.7 +/- 2.3 and 68.0 +/- 51.0 minutes (P greater than .05 vs no drug), respectively. Three cats died and two were sacrificed six hours after coronary occlusion. Blood pressure fell to 86 +/- 20 mm Hg two minutes after coronary occlusion, rose to 95 +/- 23 mm Hg at ten minutes, and remained there for ten minutes. Timolol did not alter postganglionic cardiac sympathetic neural discharge prior to coronary occlusion. Two minutes after coronary occlusion, mean postganglionic cardiac sympathetic neural discharge was 128 +/- 27 and increased to 139 +/- 36 impulses/second (% control) 4 minutes after coronary occlusion. A similar trend was found for the data recorded in 15 nerves (eight cats) in which coronary occlusion was initiated without timolol. The data suggest that a difference exists among beta blockers because prior to coronary occlusion, the cardioselective drugs metoprolol (1, 5, and 10 mg/kg, IV) and practolol (8 mg/kg, IV) depressed postganglionic cardiac sympathetic neural discharge whereas noncardioselective timolol did not. Because all three beta blockers increased the times to arrhythmia and death (although the increase was significant only after metoprolol and practolol), the acute protective mechanism does not appear to be due primarily to a depression of spontaneous sympathetic neural discharge.
Vascular access is an important step in the care of the critically ill child but can be very difficult and time consuming. Recently, intraosseous infusion has experienced a resurgence as a rapid alternative to venous cannulation. Several cases illustrate the usefulness of this technique in the emergency department. Included are the first reports of the use of intraosseous diazepam and succinylcholine.
Intravenous access for the administration of antiepileptic drugs can be both time-consuming and difficult in an actively seizing infant. We conducted a study to examine the intraosseous route as an alternate means of vascular access for the administration of diazepam in a pentylenetetrazol-seizure model in pigs. Epileptogenic activity was induced with pentylenetetrazol 100 mg/kg in 15 domestic swine that had undergone craniotomies for electrocortical recording. Diazepam (0.1 mg/kg) was administered IV (n = 5) or intraosseously (n = 5); control animals received no drug (n = 5). Epileptogenic activity was suppressed below control levels within one minute in the IV group and within two minutes in the intraosseous group. A two-way analysis of variance did not show a significant difference between the IV and intraosseous routes; however, both were significantly different when compared to the control. There also was no significant difference in plasma diazepam levels between the two groups at one, two, five, ten, 15, and 20 minutes. Our study demonstrated that the intraosseous route is a rapid and effective alternative for diazepam administration.
We conducted a study to evaluate the absorption of endotracheally administered diazepam and the pulmonary pathologic changes induced by its administration. Six cats received diazepam and five cats received saline endotracheally. Serial blood gases and serum diazepam levels were drawn at intervals for 90 minutes after the administration of diazepam. The cats were sacrificed after two days and their lungs were examined by a pathologist. Mean diazepam levels reached a peak two minutes after the administration of diazepam and remained elevated above therapeutic levels for 90 minutes. There was no significant change in pH, PO2, or PCO2 for either group. Histologic examination of the lungs showed a significantly increased incidence of pneumonitis in the diazepam group as compared to the saline group. This study demonstrates that although diazepam is well absorbed when administered endotracheally, it has adverse effects on the lungs that may preclude endotracheal use in the currently available commercial form.
The drug of choice for local anesthesia in most emergency departments is lidocaine. However, it wears off shortly after suturing is complete and patients may experience pain after closure of the wound. We conducted a study to determine the degree of anesthesia obtained during and after repair of lacerations using lidocaine 1% versus bupivacaine 0.25%, a long-acting local anesthetic. Lidocaine and bupivacaine were administered in a double-blind, randomized fashion to 104 patients. Each patient was asked to rate his pain on a 0 to 10 scale (0, no pain; 10, severe pain) prior to administration of the anesthetic. They then rated pain on an identical scale at 30 minutes, and one, two, three, four, five, six, 12, 18, and 24 hours after completion of suturing. The mean baseline pain was 2.96 for the lidocaine group and 3.07 for the bupivacaine group. This decreased to less than 1.0 in both groups 30 minutes after infiltration. It remained low for the bupivacaine group for the next five hours, but increased almost to preanesthesia levels by two hours in the lidocaine group. A three-way analysis of variance revealed a significant difference (P less than .001) between the pain response of the two groups. There was no statistical difference (P greater than .05) between the age of the patients, size of laceration, and amount of drug used. The study shows that patients do experience pain after a wound is sutured and the anesthetic has worn off. It also demonstrates that bupivacaine significantly reduces the pain a patient may experience after repair of a wound.
Five domestic swine weighing 8 to 12 kg were anesthetized with ketamine 20 mg/kg IM and pentobarbital 20 mg/kg IV. After a sterile prep each animal received NaHCO3 1 mEq/mL/kg in one tibia and saline 1 mL/kg in the other. The animals were allowed to recover and were observed for 30 days. At the end of this period, roentgenographs were obtained of each tibia and triple phase 99m technetium bone scans were obtained. The tibias also were sectioned, stained, and examined under light microscopy for microscopic abnormalities. The only deficit found was a small cortical calcification at the site of the needle puncture in an animal that received NaHCO3. All other roentgenographs, bone scans, and microscopic specimens were normal. This study demonstrates that NaHCO3 does not have permanent adverse effects when injected into the marrow cavity of swine and supports previous clinical observations regarding the safety of NaHCO3.
The effect of timolol (5 mg/kg, p.o., b.i.d. 7 or 14 days) on cardiac beta adrenergic receptor density, the times to arrhythmia (AR) and death (D), heart rate, mean arterial blood pressure, and postganglionic cardiac sympathetic neural discharge after acute coronary occlusion in cats was examined. In the control animals, receptor densities in the left and right atria did not differ, but were lower than the right ventricle. Left ventricle and septum receptor densities were higher, with the left ventricle the highest. The importance of the gradation of beta receptors with increasing density from base to apex appears to be its relation to cardiac contractile function. Occlusion in cats not treated with timolol did not alter the cardiac beta receptor densities. After timolol for 7 or 14 days, no occlusion, receptor density increased in left ventricle and septum although the increase was only significant after 14 days. A comparison of the beta adrenergic receptor densities in cats pretreated with timolol for 7 or 14 days with or without occlusion revealed that, in general, a decrease (p greater than 0.05) occurred for the occlusion group. Timolol decreased heart rate and blood pressure prior to occlusion. The mean times to AR and D were not significantly increased by either dosing regimen of timolol, although the trend was for an increase in the time to D after 7 days of timolol and an increase in the time to AR and D after 14 days of timolol. When compared with data obtained in saline cats, chronic timolol produced minimal changes in postganglionic cardiac sympathetic neural discharge. Timolol given chronically (p.o.) or acutely (5 mg/kg, i.v. given 15 min prior to occlusion) also did not prevent the cardiac sympathetic discharge associated with the development of AR. The time to AR and D in the acutely treated cats was increased but not significantly. Since cardiac sympathetic neural discharge increased as blood pressure fell in the control period but did not increase after occlusion in the timolol treated animals, the combination of timolol and occlusion may have modified neural discharge via an action on the baroreceptor mechanism. That chronic administration of timolol produces an effect not present in cats in which only occlusion was done is supported by the observation that chronic treatment produced an occlusion-induced decrease in beta adrenergic receptor density.(ABSTRACT TRUNCATED AT 400 WORDS)