Eric W. Warren

Advances in the Treatment and Prophylaxis of Pneumocystis carinii Pneumonia

Pneumocystis carinii pneumonia (PCP) is the most common illness associated with the acquired immunodeficiency syndrome (AIDS) in the United States and also occurs in immunocompromised persons not infected with the human immunodeficiency virus. Several advances have taken place in the treatment and prophylaxis of PCP, with most clinical trials conducted in patients with AIDS. Treatment of choice is trimethoprim‐sulfamethoxazole (TMP‐SMX). Desensitization regimens are available for those who have a fever or rash associated with the agent. Patients with severe PCP who cannot tolerate TMP‐SMX may be treated successfully with pentamidine or trimetrexate. Those with mild to moderate disease may receive dapsone‐trimethoprim, clindamycin‐primaquine, or atovaquone if they cannot take TMP‐SMX. Adjunctive therapy with corticosteroids improves the outcome in patients with AIDS and severe PCP. (Pharmacotherapy 1997;17(5):900–916)

Comparison of intravenous and intranasal administration of epinephrine during CPR in a canine model

STUDY OBJECTIVES Epinephrine improves coronary perfusion pressure during CPR. However, administration of epinephrine during CPR may be delayed or omitted if IV or endotracheal access is not established. Therefore, the objective of this study was to determine if intranasal administration of epinephrine during CPR would provide an alternate route of drug administration that is readily accessible and requires no special technical skills. DESIGN AND SETTING Randomized blinded study performed in a controlled laboratory environment. TYPE OF PARTICIPANTS Twenty mongrel dogs weighing 19.5 +/- 4.6 kg. INTERVENTIONS All dogs received either IV epinephrine 0.015 mg/kg or intranasal epinephrine 14 mg per nostril. Phentolamine (5 mg per nostril) was administered intranasally one minute before nasal administration of epinephrine to improve absorption. Each dog underwent three minutes of ventricular fibrillation followed by seven minutes of CPR with a pneumatic chest compression device. Epinephrine was administered at two minutes into CPR. MEASUREMENTS AND MAIN RESULTS Seven dogs were excluded because of inadequate baseline coronary perfusion pressure or compression device displacement, leaving a total of 13 dogs for analysis (six IV epinephrine, seven intranasal epinephrine). Baseline coronary perfusion pressure (mean +/- SD) was similar for IV epinephrine and intranasal epinephrine (16.9 +/- 7.1 mm Hg versus 18.2 +/- 13.8 mm Hg, respectively, P = .84). For IV and intranasal epinephrine, coronary perfusion pressure increased to 21.4 +/- 9.2 mm Hg and 24.4 +/- 18.7 mm Hg one minute after epinephrine, respectively (P = .73). Five minutes after epinephrine coronary perfusion pressure was 18.2 +/- 8.7 mm Hg and 24.3 +/- 13.9 mm Hg for IV epinephrine and intranasal epinephrine, respectively (P = .38). The rate of successful resuscitation was similar for both groups, five of seven dogs for intranasal epinephrine and four of six dogs for IV epinephrine (P = .66). CONCLUSION Intranasal epinephrine has similar effects on coronary perfusion pressure and resuscitation compared with standard-dose IV epinephrine. Therefore, the nasal route for administration of epinephrine appears to be an acceptable alternate method of drug delivery during CPR and compares favorably with standard IV therapy in the canine model. Because of the obvious benefits to human patients, these observations suggest further investigation.

The effect of sodium bicarbonate administration on the vasopressor effect of high-dose epinephrine during cardiopulmonary resuscitation in swine

Sodium bicarbonate is administered during cardiopulmonary resuscitation (CPR) for the treatment of systemic acidemia. However, the effect of administering standard-dose sodium bicarbonate on the vasopressor effect of epinephrine is unknown. This study compared the effects of sodium bicarbonate or normal saline on the vasopressor effect of epinephrine in 18 pigs. After 10 minutes of unassisted ventricular fibrillation, CPR was started using a pneumatic chest compression device. Two minutes after the start of CPR, sodium bicarbonate (1 mEq/kg) or normal saline (1 mL/kg) was administered into the right ventricule followed 1 minute later by epinephrine (0.2 mg/kg). Defibrillation was attempted at 8 minutes of CPR (18 minutes of ventricular fibrillation). Results demonstrated no significant differences in aortic systolic, aortic diastolic, or coronary perfusion pressure (CPP) between the two groups (1 minute after epinephrine, CPP was 22.6 +/- 13.3 mm Hg versus 21.1 +/- 20.7 mm Hg for the sodium bicarbonate and normal saline groups, respectively). However, when the data were stratified according to pH < 7.4 and pH > 7.4, the peak change in CPP was 12.7 +/- 21 mm Hg when pH < 7.4 and was 5.2 +/- 7.4 when pH > 7.4 (P = .33). Resuscitation was also similar between the two groups (two of nine for sodium bicarbonate and one of nine for normal saline). In conclusion, the standard recommended dose of sodium bicarbonate did not alter the vasopressor effect of epinephrine or resuscitation compared with normal saline in this closed chest model of ventricular fibrillation and CPR.

Effect of high-dose sodium bicarbonate on the vasopressor effects of epinephrine during cardiopulmonary resuscitation

We attempted to determine the effect of extreme alkalemia induced by high‐dose sodium bicarbonate on the vasopressor effects of epinephrine during cardiopulmonary resuscitation (CPR). Subjects in this randomized, blinded study performed in a controlled laboratory environment were 12 mongrel dogs that had had a previous episode of CPR. Each dog underwent 3 minutes of ventricular fibrillation (VF) followed by 7 minutes of closed‐chest CPR. Animals were assigned to receive either sodium bicarbonate 3 mEq/kg and epinephrine 0.1 mg/kg, or normal saline 3 ml/kg and epinephrine 0.1 mg/kg. The sodium bicarbonate or normal saline was infused over 2 minutes beginning at 4 minutes of VF (1 min of CPR) followed by bolus epinephrine. Arterial pH in the sodium bicarbonate group was significantly higher at each sampling point (7.7 ± 0.1 vs 7.29 ± 0.06 at 1 min after drug, p<0.001). However, there were no statistically or clinically significant differences in coronary perfusion pressure between the groups at any time: 29 ± 13 versus 32 ± 21 mm Hg 1 minute, and 22 ± 12 versus 26 ± 19 mm Hg 4 minutes after epinephrine for sodium bicarbonate and normal saline, respectively (p>0.7). Increased arterial pH (alkalemia) induced by high‐dose sodium bicarbonate administration did not improve the vasopressor effects of epinephrine during CPR in this canine model. These results suggest the limited value of administering sodium bicarbonate during CPR to improve the responsiveness to epinephrine.

Effect of dose on the nasal absorption of epinephrine during cardiopulmonary resuscitation

Abstract Delay in epinephrine administration during cardiopulmonary resuscitation (CPR) due to technical difficulties in obtaining an access site may be detrimental. To avoid this potential delay, we have previously shown that intranasal administration of phentolamine and epinephrine is a rapidly obtainable and feasible route of administration during CPR. The objective of this study was to determine the optimal dose of phentolamine and epinephrine to be administered during CPR. A randomized blinded dose ranging study was performed in a controlled laboratory environment. Thirty-six mongrel dogs were randomized to one of the following dosage regimens: phentolamine, 0.25 or 2.5 mg/kg/nostril; epinephrine, 0.075, 0.75, or 7.5 mg/kg/nostril. Phentolamine was administered intranasally 1 minute before the intranasal administration of epinephrine to improve absorption. Each dog underwent 3 minutes of ventricular fibrillation followed by 7 minutes of closed chest CPR. Epinephrine was administered at 3 minutes of CPR. Data from 26 dogs were included for analysis. Treatment B (0.25 and 7.5 mg/kg/nostril of phentolamine and epinephrine, respectively) produced the greatest elevation in coronary perfusion pressure (17 ± 11 vs 4 ± 3 mm Hg for the next highest group, P 5 5 ) versus 0% to 50% for the other groups (P

An alternative sodium bicarbonate regimen during cardiac arrest and cardiopulmonary resuscitation in a canine model

We evaluated the effect of frequent, early bolus administration of low‐dose sodium bicarbonate (NaHCO3) on blood gas values during ventricular fibrillation and cardiopulmonary resuscitation (CPR) compared with normal saline and standard bolus doses of NaHCO3. This was a randomized laboratory investigation involving 13 mongrel dogs and 18 experiments (5 dogs were used in a crossover manner). Each dog underwent 3 minutes of ventricular fibrillation, followed by 15 minutes of CPR. Animals were randomly assigned to one of three treatments administered early in the resuscitation effort: NaHCO3 0.5 mEq/kg at 5, 10, and 15 minutes of ventricular fibrillation (SB); NaHCO3 1 mEq/kg at 5 minutes and 0.5 mEq/kg at 15 minutes of fibrillation (B); or 0.9% NaCl 1 ml/kg at 5 minutes and 0.5 ml/kg at 15 minutes of fibrillation (P). A total of 15 experiments were included for analysis. Arterial and venous blood gases were sampled at 4, 8, 13, and 18 minutes of fibrillation. The SB group demonstrated the highest arterial partial pressures of carbon dioxide (pCO2) at each sampling point after NaHCO3, including the 18‐minute sample: 42 ± 12, 29 ± 11, and 35 ± 10 torr for SB, P, and B, respectively. In addition, SB produced arterial alkalemia (pH > 7.45) after NaHCO3 administration. The arterial pH at 18 minutes of fibrillation for SB, P, and B was 7.46 ± 0.14, 7.29 ± 0.07, and 7.41 ± 0.1, respectively. Similar trends for pCO2 and pH were observed for venous samples. Early, frequent administration of low‐dose NaHCO3 during CPR is associated with elevated pCO2 and pH (alkalotic) values that may be potentially detrimental in this setting. It appears that this mode of administration offers no advantage over B with regard to blood gas values during CPR in this canine model.

Effect of vehicle on the nasal absorption of epinephrine during cardiopulmonary resuscitation

Study Objectives. We have shown in previous studies that epinephrine administered intranasally is a feasible route of administration during cardiopulmonary resuscitation (CPR). To promote the absorption of epinephrine we administered phentolamine prior to epinephrine and used a bile salt as a vehicle to dissolve the epinephrine. The purpose of this study was to compare the effect of two different vehicles (bile salt vs surfactant) in promoting the absorption of nasally administered epinephrine during CPR and to determine their effects on the nasal mucosa.

Inguinal phlegmon and positive serology for syphilis after penile bite laceration: true, true and unrelated

Among many causes of penile injury, sexual activity is infrequently reported. The present case involved delay in recognition, which led to development of a phlegmon near major vascular structures. Positive serologic evidence of syphilis was an incidental finding.