Joel S. Goldberg

Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl administration.

Fentanyl, unlike morphine, is highly lipophilic and rapidly diffuses out of the epidural space. Respiratory depression is, therefore, unlikely when fentanyl is given epidurally. However, much of fentanyls analgesic effect is mediated by systemic rather than spinal receptor binding. To test this hypothesis, we performed a prospective, double-blind, cross-over study comparing epidural and intravenous (IV) administration of fentanyl in 16 patients for the first 12 h after lower abdominal or lower extremity surgery. To allow direct comparison of these two routes of administration, patient-controlled analgesia was used so patients could self-titrate their analgesia. Patients were randomized to receive fentanyl initially by an epidural (group A, n = 8) or IV (group B, n = 8) catheter for 6 h, after which they were crossed-over to the alternate route by means of a hidden three-way stopcock. The degree of analgesia was subjectively evaluated by a visual analogue scale, and by an observer rating patients comfort and sedation. Cumulative dosage of fentanyl was recorded, and plasma fentanyl concentrations were measured. The onset of analgesia and increase in plasma fentanyl concentrations were more rapid with intravenous fentanyl. However, after 60 min, analgesia (visual analogue scale 2-4 cm) or plasma fentanyl concentrations (0.3-0.7 ng/mL) did not differ between the two routes of administration. There were also no significant differences in the cumulative dosage of fentanyl within each group (epidural vs IV) or between the groups. Thus, the analgesic effects of epidural fentanyl appear largely mediated by systemic absorption. Intravenous fentanyl achieves a similar degree of analgesia and a more rapid onset of effect without the need for epidural catheterization.

Postoperative hypertension : a multicenter, prospective, randomized comparison between intravenous nicardipine and sodium nitroprusside

ObjectiveTo compare the efficacy and safety of iv nicardipine with sodium nitroprusside in the treatment of postoperative hypertension after both cardiac and noncardiac surgery. DesignMulticenter, prospective, randomized, open-label study. SettingSix tertiary referral medical centers (recovery rooms and surgical ICUs). PatientsA total of 139 patients with postoperative hypertension: iv nicardipine (n = 71), sodium nitroprusside (n = 68). InterventionAdministration of iv nicardipine or sodium nitroprusside. MeasurementsVital signs (BP, heart rate), hemodynamic variables, medication dosage, total number of dose changes, and time to achieve BP control were recorded. Main ResultsBoth medications were equally effective in reducing BP in both the cardiac and noncardiac surgical groups. Under the conditions of the study, iv nicardipine controlled hypertension more rapidly than sodium nitroprusside (iv nicardipine 14.0 ± 1.0 mins and sodium nitroprusside 30.4 ± 3.5 mins, p = .0029). The total number of dose changes required to achieve therapeutic BP response was significantly less in the iv nicardipine-treated patients (iv nicardipine 1.5 ± 0.2 vs. sodium nitroprusside 5.1 ± 1.4, p < .05). Adverse effects were observed with both drugs (iv nicardipine 7% [5/71] and sodium nitroprusside 18% [12/68] [NS]). ConclusionsIntravenous nicardipine is as effective as sodium nitroprusside in the therapy of postoperative hypertension. Specific advantages have been identified. The use of iv nicardipine should be considered in the therapy of postoperative hypertension. (Crit Care Med 1992; 20:1637–1643)

Blockade of smoking satisfaction using the peripheral nicotinic antagonist trimethaphan.

The present study was conducted to investigate the role of peripheral nicotinic receptors in mediating the rewarding effects of cigarette smoking. Twelve cigarette smokers rated cigarettes after intravenous infusion of the short-acting peripheral nicotinic receptor antagonist trimethaphan and after placebo (saline) infusions. Subjects were blinded to the infusion and cigarette conditions. Cigarette conditions included subjects usual brand of cigarette, denicotinized tobacco cigarettes, and nicotine-injected cigarettes that had a tar delivery equal to that of the denicotinized cigarettes but with an enhanced nicotine delivery equal to that of subjects usual brands. The latter cigarettes were rated as extremely harsh due to the high nicotine/tar ratio. Trimethaphan significantly attenuated the airway sensations associated with nicotine, and eliminated the difference in smoking satisfaction between the usual brand of cigarette and the other two cigarettes. These findings suggest that nicotinic receptors on peripheral nerve endings in the respiratory tract modulate smoking satisfaction and may be important in the maintenance of cigarette addiction.

Colorimetric end-tidal carbon dioxide monitoring for tracheal intubation

We evaluated a Colorimetric end-tidal carbon dioxide (ETco2) detector (FEF end-tidal carbon dioxide detector, Fenem, New York, N.Y.) during 62 intubations in anesthetized patients who were hemodynamically stable. The intubations were performed during a drill that simulates difficult tracheal intubation and therefore is associated with an increased risk of esophageal intubation. Each intubation attempt was monitored by two anesthesiologists and a research assistant who together used chest auscultation, Colorimetric ETco2, and capnography to confirm tracheal intubation and detect esophageal intubation. The reliability of the monitors was compared with capnography. Colorimetric ETco2 confirmed tracheal intubations and detected esophageal intubations 100% of the time, as judged by capnography. There were no false-positive or false-negative decisions based on endotracheal tube position; however, one equivocal color change occurred, which was caused by failure to inflate the endotracheal tube cuff. Colorimetric ETco2 monitoring confirmed tracheal intubation more rapidly than did chest auscultation (P < 0.001) or capnography (P < 0.05), and detected esophageal intubation more rapidly than did chest auscultation (P < 0.05) and as rapidly as capnography did. Confirmation of tracheal intubation VMS achieved earlier than detection of esophageal intubation with all three monitors (P < 0.05). We conclude that Colorimetric ETco2 monitoring is a safe, reliable, rapid, simple, and portable method for determining endotracheal tube position for patients who are hemodynamically stable and should be recommended where capnography is not available.

Diagnosis of obstructive airways disease from the clinical examination

AbstractObjective: To determine the operating characteristics of history and physical examination items for pulmonary airflow obstruction.n Design: Prospective observational study.n Setting: Medical Preoperative Evaluation Clinic at the Durham Veterans Affairs Medical Center.n Patients/participants: Consecutive patients referred for outpatient medical preoperative risk assessment.n Interventions: None.n Measurements and main results: Number of years the patient had smoked cigarettes, patient-reported wheezing [LR+ (likelihood ratio for finding present)=3.1; LR− (likelihood ratio for finding absent)=0.58], and auscultated wheezing (LR+=12; LR−=0.87) were independent predictors of obstructive airways disease from the history and physical examination. Forced expiratory time and peak expiratory flow rate, both measured by the clinician at the bedside, were additional independent predictors of airflow obstruction. A nomogram using patient-reported wheezing, number of years the patient had smoked, and auscultated wheezing was developed and validated (area under receiver operating characteristic curve=0.78; p=0.0001) for the bedside prediction of obstructive airways disease. Peak expiratory flow rate can be substituted for auscultated wheezing with similar predictive ability.n Conclusions: The results of bedside clinical examinations predict the presence of obstructive airways disease. A nomogram based on a combination of four bedside findings predicts airflow obstruction as well as clinicians’ overall clinical impressions.

Nicardipine infusion for postoperative hypertension after surgery of the head and neck

The therapy of postoperative hypertension (POH) after head and neck surgery was evaluated in a prospective, randomized, double-blind trial. Nicardipine hydrochloride, a Ca channel-blocker for iv use, was compared with placebo. Patients were initially randomized to receive nicardipine infusion or placebo. Those not responding to placebo were given nicardipine infusion on an open basis. Hypertension was significantly better controlled in patients treated with nicardipine infusion compared with placebo (83% vs. 22%, p less than .002). Subsequently, six (86%) of seven of the placebo failures were successfully treated with nicardipine. There were no significant complications in either group. We conclude that the titratable infusion of nicardipine is an effective and safe method for the control of POH after surgery of the head and neck. Further studies are now warranted comparing nicardipine with other drugs currently used to treat this condition.

Simulation technique for difficult intubation: Teaching tool or new hazard?

This investigation evaluated the risks of a simulation drill designed to improve the skill of anesthesia personnel in dealing with an unexpected difficult intubation. In a controlled prospective study, 40 patients with normal airways scheduled to undergo noncardiothoracic surgery were randomized into two groups of 20 patients. In the control group, intubation was performed by standard techniques. In the simulation group, intubation of a difficult airway was simulated and performed with the aid of an endotracheal tube introducer. Heart rate (HR); systolic, mean, and diastolic blood pressures (BPs); and arterial oxygen saturation were measured noninvasively during the preinduction period and 1 minute postintubation. A record was kept of all adverse events, including electrocardiogram (EKG) evidence of myocardial ischemia or cardiac arrhythmias, esophageal intubation, pulmonary aspiration, or tracheal injury. There were no significant differences in percent changes in HR, BP, or oxygen saturation between the two groups. There were five uncomplicated esophageal intubations in the simulation group compared with none in the control group (p = 0.001). No other adverse events were recorded. The potential hazards of esophageal intubation should be considered before this simulation drill is performed.

Labetalol for the control of elevated blood pressure following coronary artery bypass grafting

In a multicenter study, the efficacy and safety of intravenous (IV) labetalol for the control of elevated blood pressure were studied in the intensive care unit (ICU) in 65 patients within 4 hours following coronary artery bypass grafting (CABG). Patients with pre-existing ventricular dysfunction, bradycardia, bronchospastic disease, or postoperative complications were excluded. All patients were monitored with a thermodilution pulmonary artery catheter. Entry criteria were a systolic blood pressure (SBP) greater than 140 mm Hg or diastolic blood pressure (DBP) greater than 90 mm Hg for at least five minutes. Intravenous labetalol was loaded incrementally (5, 10, 20, and 40 mg at 10-minute intervals) to a maximum cumulative dose of 75 mg, until either SBP decreased 10% or DBP decreased 10% and was less than 90 mm Hg. Responders were entered into a 6-hour maintenance period, and received 5 to 40 mg of IV labetalol every 10 minutes as needed for blood pressure control. Hemodynamic data and temperature were recorded at baseline, just before each dose of labetalol during the loading period, and at the end of the maintenance period. Alternative therapy was given in the case of nonresponse or adverse events. Intravenous labetalol successfully controlled post-CABG hypertension in 55 of 65 patients (85%); of these, 46 responded to 35 mg or less. Although 28 patients required no further labetalol in the maintenance period, in the others dosage varied from 5 to 400 mg. Reductions in SBP and DBP were associated with moderate reductions in pulse pressure (SBP-DBP) and heart rate (HR). Cardiac index decreased by 18.5%, with a 12.5% decrease in stroke index and 8.1% decrease in HR. Systemic vascular resistance did not increase significantly. Four patients (6%) developed hypotension related to IV labetalol. There was one death due to perioperative myocardial infarction, which was unrelated to labetalol use. The mechanism of action of IV labetalol in controlling hypertension after CABG surgery seems to be moderate negative inotropy and chronotropy. Its alpha-blocking effects seem to be important in preventing reflex vasoconstriction. This is directly opposite to the primary vasodilator effect found when IV labetalol is used to control nonsurgical hypertension. Because of these actions, labetalol should be avoided or used with caution in patients with preoperative and postoperative cardiac dysfunction. In patients with normal left ventricular function, IV labetalol appears to be a safe, effective agent in controlling post-CABG hypertension, with the added potential benefit of enhanced myocardial oxygen balance.

Revisiting the Monoamine Hypothesis of Depression: A New Perspective

As the incidence of depression increases, depression continues to inflict additional suffering to individuals and societies and better therapies are needed. Based on magnetic resonance spectroscopy and laboratory findings, gamma aminobutyric acid (GABA) may be intimately involved in the pathophysiology of depression. The isoelectric point of GABA (pI = 7.3) closely approximates the pH of cerebral spinal fluid (CSF). This may not be a trivial observation as it may explain preliminary spectrophotometric, enzymatic, and HPLC data that monoamine oxidase (MAO) deaminates GABA. Although MAO is known to deaminate substrates such as catecholamines, indoleamines, and long chain aliphatic amines all of which contain a lipophilic moiety, there is very good evidence to predict that a low concentration of a very lipophilic microspecies of GABA is present when GABA pI = pH as in the CSF. Inhibiting deamination of this microspecies of GABA could explain the well-established successful treatment of refractory depression with MAO inhibitors (MAOI) when other antidepressants that target exclusively levels of monoamines fail. If further experimental work can confirm these preliminary findings, physicians may consider revisiting the use of MAOI for the treatment of non-intractable depression because the potential benefits of increasing GABA as well as the monoamines may outweigh the risks associated with MAOI therapy.

Chronic Opioid Therapy and Opioid Tolerance: A New Hypothesis

Opioids are efficacious and cost-effective analgesics, but tolerance limits their effectiveness. This paper does not present any new clinical or experimental data but demonstrates that there exist ascending sensory pathways that contain few opioid receptors. These pathways are located by brain PET scans and spinal cord autoradiography. These nonopioid ascending pathways include portions of the ventral spinal thalamic tract originating in Rexed layers VI–VIII, thalamocortical fibers that project to the primary somatosensory cortex (S1), and possibly a midline dorsal column visceral pathway. One hypothesis is that opioid tolerance and opioid-induced hyperalgesia may be caused by homeostatic upregulation during opioid exposure of nonopioid-dependent ascending pain pathways. Upregulation of sensory pathways is not a new concept and has been demonstrated in individuals impaired with deafness or blindness. A second hypothesis is that adjuvant nonopioid therapies may inhibit ascending nonopioid-dependent pathways and support the clinical observations that monotherapy with opioids usually fails. The uniqueness of opioid tolerance compared to tolerance associated with other central nervous system medications and lack of tolerance from excess hormone production is discussed. Experimental work that could prove or disprove the concepts as well as flaws in the concepts is discussed.