Vasopressin for Cardiac Resuscitation; Predictive Value of Nitro Relief; Desaturation, Pulse Reactivity in RSI

Vasopressin for Cardiac Resuscitation

Wenzel V, Krismer AC, Arntz HR, et al. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 350(2):105–13, Jan. 8, 2004.

Abstract: Background-Vasopressin is an alternative to epinephrine for vasopressor therapy during cardiopulmonary resuscitation, but clinical experience with this treatment has been limited. Methods-The authors randomly assigned adults who'd had an out-of-hospital cardiac arrest to receive two injections of either 40 IU of vasopressin or 1 mg of epinephrine, followed by additional treatment with epinephrine if needed. The primary endpoint was survival to hospital admission, and the secondary endpoint was survival to hospital discharge.

Results-A total of 1,219 patients underwent randomization; 33 were excluded because of missing study-drug codes. Among the remaining 1,186 patients, 589 were assigned to receive vasopressin and 597 to receive epinephrine. The two treatment groups had similar clinical profiles. There were no significant differences in the rates of hospital admission between the vasopressin group and the epinephrine group either among patients with ventricular fibrillation (46.2% vs. 43.0%, P=0.48) or among those with pulseless electrical activity (33.7% vs. 30.5%, P=0.65). Among patients with asystole, however, vasopressin use was associated with significantly higher rates of hospital admission (29.0% vs. 20.3% in the epinephrine group; P=0.02) and hospital discharge (4.7% vs. 1.5%, P=0.04). Among 732 patients in whom spontaneous circulation was not restored with the two injections of the study drug, additional treatment with epinephrine resulted in significant improvement in the rates of survival to hospital admission and hospital discharge in the vasopressin group, but not in the epinephrine group (hospital admission rate, 25.7% vs. 16.4%; P=0.002; hospital discharge rate, 6.2% vs. 1.7%; P=0.002). Cerebral performance was similar in the two groups.

Conclusions-The effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine may be more effective than epinephrine alone in the treatment of refractory cardiac arrest.

Comment: We are all frustrated with our inability to resuscitate more patients who are in cardiac arrest, and vasopressin is the most recent medication to show some promise. In this study, the overall group did not benefit from vasopressin. However, for the patients in asystole, 12 who received vasopressin survived to hospital discharge, compared to four in the epinephrine group.

There were a number of problems with this study design. One of the most important was that the authors did not say how many of those who were discharged were comatose or otherwise severely brain-injured. We know that four of the five who did not receive CPR remained comatose at the time of discharge, but do not know about the other 12. We tend to think of hospital discharge as synonymous with going home, but in cardiac arrest studies, that is often not the case. Many remain in vegetative states in long-term care facilities. The authors correctly concluded that a new study looking only at patients in asystole was needed to determine the true value of vasopressin.

Unfortunately, the accompanying editorial (McIntyre KM. Vasopressin in asystolic cardiac arrest. NEJM 350(2):179–80) dramatically overstated the significance of these results. By claiming that this was an "important breakthrough in the science of resuscitation" and that "medical policymakers should facilitate [vasopressin's] orderly implementation," the editorial's author attracted much misguided media attention. In fact, this is a preliminary work that only serves as the foundation for a future trial. Vasopressin may have some benefit in some patients, but it is premature to conclude at this time that it should be used in cardiac arrest.

Predictive Value of Nitro Relief

Henrikson CA, Howell EE, Bush DE, et al. Chest pain relief by nitroglycerin does not predict active coronary artery disease. Ann Intern Med 139(12):979–86, Dec. 16, 2003.

Abstract: Background-The belief that chest pain relief with nitroglycerin indicates the presence of active coronary artery disease is common. However, this hypothesis has not been tested. Objective-To define the diagnostic and prognostic value of chest pain relief with nitroglycerin. Design-Prospective observational cohort study. Setting-Urban community teaching hospital. Patients-459 consecutive patients with chest pain admitted through the emergency department who received nitroglycerin from emergency services personnel or an emergency department nurse. Follow-up was obtained by telephone contact at four months. Measurements-Chest pain relief was defined as a decrease of at least 50% in patients' self-reported pain within five minutes of the initial dose of sublingual or spray nitroglycerin. Active coronary artery disease was defined as any elevated serum enzyme levels, coronary angiography demonstrating a 70% or greater stenosis, or a positive exercise test result.

Results-Nitroglycerin relieved chest pain in 39% of patients (181 of 459). In patients with active coronary artery disease as the likely cause of their chest pain, 35% (49 of 141) had chest pain relief with nitroglycerin. In contrast, in patients without active coronary artery disease, 41% (113 of 275) had chest pain relief (P>0.2). Four-month clinical outcomes were similar in patients with or without chest pain relief with nitroglycerin (P>0.2).

Conclusions-These data suggest that, in a general population admitted for chest pain, relief of pain after nitroglycerin treatment does not predict active coronary artery disease and should not be used to guide diagnosis.

Comment: This is one of those "facts" of patient evaluation we all learn in medical, nursing, paramedic and EMT school: If someone has chest pain and it goes away with an NTG or two, then it was likely due to myocardial ischemia (angina or heart attack). This study is good evidence that this "fact" may be just another myth. Of course, it does not say that the relief of chest pain with NTG suggests that the pain was not from myocardial ischemia, either. We need to understand that the NTG gives us no additional information, and that we must assume that chest pain is due to myocardial ischemia until we can prove otherwise.

Desaturation, Pulse Reactivity in RSI

Dunford JV, Davis DP, Ochs M, et al. Incidence of transient hypoxia and pulse rate reactivity during paramedic rapid sequence intubation. Ann Emerg Med 42(6):721–8, Dec. 2003.

Abstract: Study Objective-To determine the incidence of desaturation and pulse rate reactivity during paramedic rapid sequence intubation of patients with severe head injuries (Glasgow Coma Scale score < or = 8). Methods-Adult patients with severe head injuries had recording oximeter-capnometers applied before rapid sequence intubation. Desaturation was defined as a reduction in oxygen saturation (SpO2) to less than 90% from an initial SpO2 of greater than or equal to 90%, or a decrease from a baseline of less than 90%. Event records were analyzed with emergency medical services run sheets and debriefing reports. Results-Thirty-one (57%) of 54 patients demonstrated desaturation during rapid sequence intubation. Twenty-six (84%) of these 31 events occurred in patients whose initial SpO2 value with basic airway skills was greater than or equal to 90%. The median duration of desaturation was 160 seconds (interquartile range 48–272 seconds), and the median decrease in SpO2 was 22%. Six (19%) patients experienced marked bradycardia (pulse rate < 50 bpm) during desaturation events. Paramedics described rapid sequence intubation as "easy" in 26 (84%) of 31 patients with desaturation.

Conclusion-Out-of-hospital rapid sequence intubation by paramedics was complicated by a concerning incidence of desaturation and bradycardia. Paramedic reports did not reflect the presence of these concerning derangements. Most patients had acceptable SpO2 values before rapid sequence intubation. An effective strategy for preoxygenation is needed before it can be concluded that rapid sequence intubation is of value in the out-of-hospital care of patients with serious closed head injury.

Comment: I have commented in previous columns about the rapid sequence intubation trial in San Diego, where it was found that the patients who had RSI had a higher incidence of death and other poor outcomes. This study may give us one answer as to why that was the case. Many patients who were reported to have uncomplicated procedures were later found-by recording oximeters and capnometers-to have significant and prolonged episodes of hypoxia and CO2 fluctuations. EMS systems that perform RSI should be looking carefully not only at their outcomes, but also at the continuous measurement of O2 and CO2 during these procedures for later review and QI actions.