Improved resuscitation outcome in emergency medical systems with increased usage of sodium bicarbonate during cardiopulmonary resuscitation.

BACKGROUND: The use of sodium bicarbonate (SB) in cardiopulmonary resuscitation (CPR) is controversial. This study analyzes the effects of SB use on CPR outcome in the Brain Resuscitation Clinical Trial III (BRCT III), which was a multicenter randomized trial comparing high-dose to standard-dose epinephrine during CPR. Sodium bicarbonate use in BRCT III was optional. METHODS: The entire BRCT III database was reviewed. Analysis included only patients who arrested out of the hospital and whose time from collapse to initiation of ACLS was no longer than 30 min (total n = 2122 patients). Sodium bicarbonate use by the 16 participating study sites was analyzed. The study sites were divided according to their SB usage profile: 'low SB user' sites administered SB in less than 50% of CPRs and their first epinephrine to SB time exceeded 10 min; and 'high SB user' sites used SB in over 50% of CPRs and their first epinephrine to SB time was <10 min. RESULTS: Sites' SB usage rates ranged between 3.1% and 98.2% of CPRs. Sodium bicarbonate usage rates correlated inversely with the sites' intervals from collapse (r = - 0.579 P = 0.018) from initiation of ACLS (r = - 0.685 P = 0.003) and from first epinephrine (r = - 0.611 P = 0.012) to SB administration. Mean ROSC rate in the 'high SB user' sites was 33.5% (CI = 30.0-37.0) compared to 25.7% (CI = 23.1-28.4) in the 'low SB user' sites. In the 'high SB user' sites, hospital discharge rate was 5.3% (CI = 3.6-7.0) compared to 3% (CI = 2.0-4.0) in the 'low SB user' sites, and 5.3% (CI = 3.6-7.0) had a favorable neurological outcome compared to 2.1% (CI = 1.2-3.0) in the 'low SB user' sites. Collapse to ACLS interval was 8.5 min (CI = 8.1-9.0) in the 'high SB user' sites compared to 10.2 min (CI = 9.8-10.6) in the 'low SB user' sites, and their ACLS to first epinephrine interval was 7.0 min (CI = 6.5-7.5) compared to 9.7 min (CI = 9.3-10.2). Multivariate regression analysis found that belonging to 'high SB user' sites independently increased the chances for ROSC (OR 1.36, CI 1.08-1.7) and for achieving a good neurological outcome (OR 2.18, CI 1.23-3.86). CONCLUSIONS: Earlier and more frequent use of SB was associated with higher early resuscitability rates and with better long-term outcome. Sodium bicarbonate may be beneficial during CPR, and it should be subjected to a randomized clinical trial.

Cardiopulmonary resuscitation: what cost to cheat death?

OBJECTIVES: To review the various outcomes from cardiopulmonary resuscitation (CPR), the factors that influence these outcomes, the costs associated with CPR, and the application of cost-analyses to CPR. DATA SOURCES: Data used to prepare this article were drawn from published articles and work in progress. STUDY SELECTION: Articles were selected for their relevance to the subjects of CPR and cost-analysis by MEDLINE keyword search. DATA EXTRACTION: The authors extracted all applicable data from the English literature. DATA SYNTHESIS: Cost-analysis studies of CPR programs are limited by the high variation in resources consumed and attribution of cost to these resources. Furthermore, cost projections have not been adjusted to reflect patient-dependent variation in outcome. Variation in the patient's underlying condition, presenting cardiac rhythm, time to provision of definitive CPR, and effective perfusion all influence final outcome and, consequently, influence the cost-effectiveness of CPR programs. Based on cost data from previous studies, preliminary estimates of the cost-effectiveness of CPR programs for all 6-month survivors of a large international multicenter collaborative trial are $406,605.00 per life saved (range $344,314.00 to $966,759.00), and $225,892.00 per quality-adjusted-life-year (range $191,286.00 to $537,088.00). CONCLUSIONS: Reported outcome from CPR has varied from reasonable rates of good recovery, including return to full employment to 100% mortality. Appropriate CPR is encouraged, but continued widespread application appears extremely expensive.

Cerebral resuscitation from cardiac arrest: treatment potentials.

In 1961, in Pittsburgh, PA, "cerebral" was added to the cardiopulmonary resuscitation system (CPR --> CPCR). Cerebral recovery is dependent on arrest and cardiopulmonary resuscitation times, and numerous factors related to basic, advanced, and prolonged life support. Postischemic-anoxic encephalopathy (the cerebral postresuscitation disease or syndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of special, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based on mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limit for neurologic recovery after 5 mins of arrest must be extended to achieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinically relevant cardiac arrest-intensive care outcome models in large animals. These studies are expensive, but essential, because positive treatment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clinical trials of CPCR are limited in their ability to statistically document the effectiveness of treatments found to be beneficial in controlled outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusion overcomes multifocal no-reflow and improves outcome. Physical combination treatments, such as mild resuscitative (early postarrest) hypothermia (34 degrees C) plus cerebral blood flow promotion (e.g., with hypertension, hemodilution, and normocapnia), each having multiple beneficial effects, achieved complete functional and near-complete histologic recovery of the dog brain after 11 mins of normothermic, ventricular fibrillation cardiac arrest. Calcium entry blockers appear promising as a treatment for postischemic-anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have failed to improve neurologic outcome. Assembling and evaluating combination treatments in further animal studies and determining clinical feasibility inside and outside hospitals are challenges for the near future. Treatments without permanent beneficial effects may at least extend the therapeutic window. All of these investigations will require coordinated efforts by multiple research groups, pursuing systematic, multilevel research--from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about optimizing extracerebral life support for cerebral outcome.

Old age does not negate good cerebral outcome after cardiopulmonary resuscitation: analyses from the brain resuscitation clinical trials. The Brain Resuscitation Clinical Trial I and II Study Groups.

OBJECTIVE: To assess survival after cardiac arrest and to determine whether age is an independent determinant of late mortality or poor neurologic outcome. DESIGN: Analyses using results of Brain Resuscitation Clinical Trial I (1979 to 1984) and Brain Resuscitation Clinical Trial II (1984 to 1989), two randomized, double-blind studies of outcome following cardiac arrest. SETTING: A multicenter study in 12 acute care hospitals in nine countries (Brain Resuscitation Clinical Trial I), and 24 hospitals in eight countries (Brain Resuscitation Clinical Trial II). PATIENTS: A total of 774 patients who were initially comatose after successful resuscitation from cardiac arrest. The analyses include both in- and out-of-hospital cardiac arrests. RESULTS: The 6-month mortality rate for the entire group was 81%. Mortality rate was 94% for the oldest group (> 80 yrs) compared with 68% for the youngest group (< or = 45 yrs) (p < .01). Other independent predictors of mortality were history of diabetes mellitus, inhospital arrests, arrest time of > 5 mins, history of congestive heart failure, a noncardiac cause of arrest, and cardiopulmonary resuscitation time of > 20 mins. Of the 774 patients, 27% recovered good neurologic function. There was no statistically significant difference in neurologic recovery rates by age. Multivariate analysis showed that independent predictors of good neurologic recovery were: no history of diabetes mellitus, a cardiac cause of arrest, short arrest time, and short cardiopulmonary resuscitation time. CONCLUSION: Increasing age was a factor in postresuscitation mortality, but was not an independent predictor of poor neurologic outcome.

Pathophysiologic and therapeutic implications of acid-base changes during CPR.

Acid-base changes occurring during cardiac arrest and subsequent CPR are related to a complex low-perfusion state characterized clinically by venous and tissue hypercarbic and metabolic (lactic) acidosis. This low-flow state is a dynamic process dependent on the time intervals between onset of arrest, initiation of CPR, and restoration of adequate spontaneous circulation. Increased release of CO2 from ischemic tissues and reduced CO2 transport from the tissues to the lungs result in profound tissue acidosis. However, recent experimental data suggest that even very low pH is compatible with neurologically intact survival. Thus, the clinical use of buffer agents, and especially of sodium bicarbonate, is currently controversial. Because results of controlled clinical studies are not available, a careful review of well-performed experimental studies is necessary. So far, the use of either CO2-generating or CO2-consuming buffers has not been proved conclusively to increase neurologically intact long-term survival after CPR. More importantly, adequate ventilation and effective chest compressions must be quickly established after cardiac arrest. This will counterbalance the hypercarbic and metabolic acidemia of cardiac arrest by creating concurrent hypocarbic arterial alkalemia during at least the early phase of CPR. Thus, the treatment of the complex acid-base changes associated with CPR is based primarily on the classical maneuvers of A and B (airway and breathing = adequate oxygenation and ventilation), C (chest compressions), and D (early defibrillation for rapid restoration of spontaneous circulation). In cases of prolonged cardiac arrest or preexisting metabolic acidemia, buffer therapy may be indicated.

Simpson's paradox and clinical trials: what you find is not necessarily what you prove.

Expensive clinical trials have become the gold standard for evaluating the efficacy of promising new therapeutic agents. Full exploration of the collected data is routine to maximize the yield of the information available. However, potential methodologic flaws in these extensive analyses may not be appreciated by investigators or readers. One such problem with subgroup analyses is discussed, using hypothetical examples and data from a recently completed clinical trial of brain resuscitation as illustrations.

The use of time lines and life lines in work with chronically mentally ill people.

This article describes the use of two treatment tools, time lines and life lines, designed to be used with adults who have had lifelong experience with severe and persistent mental illness. The premise of work with these clients is that their developmental stages and tasks have been skewed by years of mental illness. By graphically charting their reminiscence of life events, many clients can be helped to integrate into society and to resolve negative life experiences. Examples are given for the use of these tools with clients and with family members.

Deferred consent: use in clinical resuscitation research. Brain Resuscitation Clinical Trial II Study Group.

Deferred consent, a new approach to the requirement for informed consent in clinical research, was used in a randomized clinical trial of brain resuscitation after cardiac arrest. Because patients were comatose and therapy had to be initiated immediately, traditional prospective consent usually could not be obtained. Using the deferred consent mechanism, family members were contacted after the first dose of experimental drug or placebo was administered and asked to consent for continued study participation. The vast majority of families were satisfied with the deferred consent mechanism. Their main concerns were about the safety of the experimental drug and whether the active drug or placebo was given. The concepts of randomization, blinding, and placebo-treated controls were generally not well understood. Although our experiences confirmed the impracticality of attempting to obtain traditional prospective consent in clinical resuscitation research, deferred consent was found to be a reasonable solution.

Emergency cardiopulmonary bypass for resuscitation from prolonged cardiac arrest.

After cardiac arrest (no flow) of more than approximately 5 minutes' duration, standard external cardiopulmonary resuscitation (CPR) basic, advanced, and prolonged life support (BLS, ALS, PLS) do not reliably produce cerebral and coronary perfusion pressures to maintain viability and achieve stable spontaneous normotension; nor do they provide prolonged control over pressure, flow, composition, and temperature of blood. Since these capabilities are often needed to achieve conscious survival, emergency closed-chest cardiopulmonary bypass (CPB) by veno-arterial pumping via oxygenator is presented in this review as a potential addition to ALS-PLS for selected cases. In six dog studies by the Pittsburgh group (n = 221; 1982 through 1988), all 179 dogs that received CPB after prolonged cardiac arrest (no flow) or after CPR (low flow) states had restoration of stable spontaneous circulation. The use of CPB enhanced survival and neurological recovery over those achieved with CPR-ALS attempts only. With CPB and standard intensive care, it was possible to reverse normothermic ventricular fibrillation (VF) cardiac arrest (no flow) of up to 15 minutes and to achieve survival without neurologic deficit; VF of 20 minutes to achieve survival but with neurologic deficit; and VF of 30 minutes to achieve transient restoration of spontaneous circulation followed by secondary cardiac death. CPB could restore stable spontaneous circulation after ice water submersion of up to 90 minutes. Other groups' laboratory and clinical results agree with these findings in general. Clinical feasibility trials are needed to work out logistic problems and to meet clinical challenges. Future possibilities for emergency CPB require further research and development.