Early interventions in severe sepsis and septic shock: a review of the evidence one decade later.

The outcomes of acute myocardial infarction, trauma, and stroke have improved by implementing processes that provide early diagnosis and aggressive interventions at the most proximal point of disease presentation. A common feature in these conditions is the implementation of early intervention strategies. One decade ago, a similar approach to sepsis began when a prospective randomized trial compared early goal-directed therapy (EGDT) to standard care using specific criteria for the early identification of high risk patients with infection. The components of EGDT were derived from expert consensus opinion to produce a protocol to reverse the hemodynamic perturbations of hypovolemia, vasodysregulation, myocardial suppression and increased metabolic demands for patients with severe sepsis in the intensive care unit (ICU). However, EGDT was provided at the most proximal phase of disease presentation in the Emergency Department (ED). With EGDT, a reduction in mortality of over 16% was shown over standard care. Since the EGDT study was published a decade ago, significant emphasis worldwide has been placed on a comprehensive approach to the first 6 hours of sepsis management which is commonly referred to as the resuscitation bundle (RB). The RB consists of early diagnosis, risk stratification using lactate levels, hemodynamic response after a fluid challenge, antibiotics, source control and hemodynamic optimization or EGDT. This review will examine one decade of evidence for the components of the RB examining its impact on systemic inflammation, the progression of organ failure, health care resource consumption and mortality in severe sepsis and septic shock.

Emergency department overcrowding in the United States: an emerging threat to patient safety and public health.

Numerous reports have questioned the ability of United States emergency departments to handle the increasing demand for emergency services. Emergency department (ED) overcrowding is widespread in US cities and has reportedly reached crisis proportions. The purpose of this review is to describe how ED overcrowding threatens patient safety and public health, and to explore the complex causes and potential solutions for the overcrowding crisis. A review of the literature from 1990 to 2002 identified by a search of the Medline database was performed. Additional sources were selected from the references of the articles identified. There were four key findings. (1) The ED is a vital component of America's health care "safety net". (2) Overcrowding in ED treatment areas threatens public health by compromising patient safety and jeopardising the reliability of the entire US emergency care system. (3) Although the causes of ED overcrowding are complex, the main cause is inadequate inpatient capacity for a patient population with an increasing severity of illness. (4) Potential solutions for ED overcrowding will require multidisciplinary system-wide support.

Central venous oxygen saturation monitoring in the critically ill patient.

In the initial treatment of a critically ill patient, blood pressure, heart rate, urine output, and central venous pressure guide resuscitative efforts. Despite normalization of these variables, global tissue hypoxia may still persist and has been implicated in the development of multiorgan failure and increased mortality. Definitive management includes intensive care unit admission, pulmonary artery catheterization using mixed venous oxygen saturation (SvO2), and hemodynamic optimization. In the absence of or before definitive management, hemodynamic optimization can be performed using central venous oxygen saturation (ScvO2) as a surrogate. The physiology, technology, clinical uses, and rationale for ScvO2 monitoring are reviewed, including issues regarding physiologic equivalence to SvO2. The clinical use of ScvO2 monitoring, evidence-based outcome implications, and limitations of ScvO2 monitoring will also be examined.

Adrenal insufficiency in high-risk surgical ICU patients.

STUDY OBJECTIVES: To examine the incidence and response to treatment of adrenal insufficiency (AI) in high-risk postoperative patients. DESIGN: Prospective observational case series. SETTING: Large urban tertiary-care surgical ICU (SICU). PARTICIPANTS: Adults > 55 years of age who required vasopressor therapy after adequate volume resuscitation in the immediate postoperative period. INTERVENTIONS: Each patient underwent a cosyntropin (ACTH) stimulation test; at the discretion of the clinical team, some patients were empirically given hydrocortisone (100 mg IV q8h for three doses) before serum cortisol values became available. MEASUREMENTS: Adrenal dysfunction (AD), defined as serum cortisol < 20 microg/dL at all time points, with Delta cortisol (60 min post-ACTH minus baseline) of < or = 9 microg/dL; functional hypoadrenalism (FH), defined as serum cortisol < 30 microg/dL at all time points or Delta cortisol (60 min post-ACTH minus baseline) < or = 9 microg/dL; and AI, as the presence of either AD or FH. RESULTS: One hundred four patients were enrolled with a mean age (SD) of 65.2 +/- 16.9 years. AI (AD plus FH) was found in 34 of 104 patients (32.7%): AD was found in 9 patients (8.7%), FH in 25 patients (24%), and normal adrenal function in 70 patients (67.3%). The absolute eosinophil count was significantly higher in the combined AD and FH groups compared with the group with normal adrenal function (p < 0.05). Forty-six of 104 patients (44.2%) received hydrocortisone; 29 (63%) could be weaned from treatment with vasopressors within 24 h. This beneficial effect of hydrocortisone reached statistical significance in the FH group when compared with untreated patients (p < 0.031); a similar trend was seen in the AD group (p = 0.083). Mortality was also lower in the hydrocortisone-treated AI patients (5 of 23 [21%] vs 5 of 11 [45%] in those not receiving hydrocortisone; p < 0.01). CONCLUSION: There is a high incidence of AI among SICU patients > 55 years of age with postoperative hypotension requiring vasopressors. There is also a significant association between hydrocortisone replacement therapy, resolution of vasopressor requirements, and improved survival.

Critical care in the emergency department: A physiologic assessment and outcome evaluation.

OBJECTIVES: The changing landscape of health care in this country has seen an increase in the delivery of care to critically ill patients in the emergency department (ED). However, methodologies to assess care and outcomes similar to those used in the intensive care unit (ICU) are currently lacking in this setting. This study examined the impact of ED intervention on morbidity and mortality using the Acute Physiology and Chronic Health Evaluation (APACHE II), the Simplified Acute Physiology Score (SAPS II), and the Multiple Organ Dysfunction Score (MODS). METHODS: This was a prospective, observational cohort study over a three-month period. Critically ill adult patients presenting to a large urban ED and requiring ICU admission were enrolled. APACHE II, SAPS II, and MODS scores and predicted mortality were obtained at ED admission, ED discharge, and 24, 48, and 72 hours in the ICU. In-hospital mortality was recorded. RESULTS: Eighty-one patients aged 64 +/- 18 years were enrolled during the study period, with a 30.9% in-hospital mortality. The ED length of stay was 5.9 +/- 2.7 hours and the hospital length of stay was 12.2 +/- 16.6 days. Nine (11.1%) patients initially accepted for ICU admission were later admitted to the general ward after ED intervention. Septic shock was the predominant admitting diagnosis. At ED admission, there was a significantly higher APACHE II score in nonsurvivors (23.0 +/- 6.0) vs survivors (19.8 +/- 6.5, p = 0.04), while there was no significant difference in SAPS II or MODS scores. The APACHE II, SAPS II, and MODS scores were significantly lower in survivors than nonsurvivors throughout the hospital stay (p

The clinical utility of serologic markers in the evaluation of the acute scrotum.

OBJECTIVE: To examine the presence of interleukin-1 (IL-1), interleukin-6 (IL-6), and creatine phosphokinase-MM (CPK-MM) in patients with acute scrotal pain and assess their clinical utility in the diagnosis of testicular torsion (TT) and epididymitis. METHODS: Twenty-five patients with acute scrotal pain were prospectively enrolled over a two-year period. History, physical examination, complete blood count, urinalysis, and scrotal ultrasound were performed. Testicular torsion was confirmed by surgical exploration. Epididymitis was diagnosed using physical examination, scrotal ultrasound, and positive urinalysis. Venous blood was assayed for IL-1, IL-6, and CPK-MM in triplicate during the routine drawing of blood in the emergency department. The data are reported as medians +/- interquartile ranges (IQRs). RESULTS: Twenty-five patients with acute scrotal pain were evaluated; 11 with TT, three with torsion of the appendix testis (TAT), ten with epididymitis, and one with varicocele. One patient had both TT and epididymitis. Interleukin-1 was not detectable in either group. The CPK-MM values between TT and epididymitis were virtually identical at 99.8 and 100 IU/L, respectively. The median value for IL-6 was 1. 03 (IQR = 0.19 to 2.86) vs 20.86 (IQR = 2.14 to 65.50) pg/mL in the torsion and epididymitis groups, respectively. The 97.5% CI for the difference of medians of 19.9 was 0.4 to 65.1, p = 0.02. Using receiver operating characteristic (ROC) curve analysis for IL-6, the area under the curve was 0.82 for torsion and 0.67 for epididymitis. Using a cutoff value of IL-6 >/= 1.41 pg/mL, the positive predictive value of IL-6 in diagnosing epididymitis was 78.6%, with a negative predictive value of 100% for TT. There were no cases of missed TT on follow-up. CONCLUSIONS: This preliminary investigation of serologic markers demonstrates that IL-6 is significantly elevated in epididymitis as compared with TT. Creatine phosphokinase-MM and IL-1 were not found to be of diagnostic utility. The small sample size of this study precludes a definitive conclusion as to the utility of these markers in the emergency department. However, IL-6 may be clinically useful as an additional element in differentiating the causes of acute scrotal pain, and further study is warranted.

Adrenal dysfunction in hemodynamically unstable patients in the emergency department.

OBJECTIVE: Adrenal failure, a treatable condition, can have catastrophic consequences if unrecognized in critically ill ED patients. The authors' objective was to prospectively study adrenal function in a case series of hemodynamically unstable (high-risk) patients from a large, urban ED over a 12-month period. METHODS: In a prospective manner, critically ill adult patients presenting to the ED were enrolled when presenting with a mean arterial blood pressure < or =60 mm Hg requiring vasopressor therapy for more than one hour after receiving fluid resuscitation (central venous pressure of 12-15 mm Hg or a minimum of 40 mL/kg of crystalloid). Patients were excluded if presenting with hemorrhage, trauma, or AIDS, or if steroids were used within the previous six months. An adrenocorticotropic hormone (ACTH) stimulation test was performed and serum cortisol was measured. Treatment for adrenal insufficiency was not instituted. RESULTS: A total of 57 consecutive patients were studied. Of these, eight (14%) had baseline serum cortisol concentrations of <20 microg/dL (<552 nmol/L), which was considered adrenal insufficiency (AI). Three additional patients (5%) had subnormal 60-minute post-ACTH-stimulation cortisol responses (<30 microg/dL) and a delta cortisol < or =9 microg/dL, which is the difference between the baseline and 60-minute levels. This is functional hypoadrenalism (FH). There were no laboratory abnormalities that distinguished patients with AI or FH from those with preserved adrenal function (PAF). Rates of survival to discharge did not differ between the AI group (7 of 8) and PAF patients (21 of 46; p = 0.052). CONCLUSIONS: Adrenal dysfunction is common in high-risk ED patients. Overall, it has a frequency of 19% among a homogeneous population of hemodynamically unstable vasopressor-dependent patients. The effect of physiologic glucocorticoid replacement in this setting remains to be determined.

Emergency department cardiopulmonary bypass in the treatment of human cardiac arrest.

OBJECTIVE: To study the use of emergency department (ED) femoro-femoral cardiopulmonary bypass (CPB) in the resuscitation of medical cardiac arrest patients. DESIGN: Prospective, uncontrolled trial. SETTING: Urban academic ED staffed with board-certified emergency physicians (EPs). PARTICIPANTS: Ten patients with medical cardiac arrest unresponsive to standard therapy. INTERVENTIONS: Femoro-femoral CPB instituted by EPs. RESULTS: The time of cardiac arrest prior to CPB (mean+/-SD) was 32.0+/-13.6 min. The cardiac output while on CPB was 4.09+/-1.03 L/min with an average of 229+/-111 min on bypass. All 10 patients had resumption of spontaneous cardiac activity while on CPB. Seven of these were weaned from CPB with intrinsic spontaneous circulation. Of these, six patients were transferred from the ED to the operating room for cannula removal and vessel repair while the other patient died in the ED soon after discontinuing CPB. Mean survival was 47.8+/-44.7 h in the six patients leaving the ED. Although these patients had successful hemodynamic resuscitation, there were no long-term survivors. CONCLUSION: CPB instituted by EPs is feasible and effective for the hemodynamic resuscitation of cardiac arrest patients unresponsive to advanced cardiac life support therapy. Future efforts need to focus on improving long-term outcome.

Vasopressin can increase coronary perfusion pressure during human cardiopulmonary resuscitation.

OBJECTIVES: To determine the hemodynamic effect of vasopressin on coronary perfusion pressure (CPP) in prolonged human cardiac arrest. METHODS: A prospective, open-label clinical trial of vasopressin during cardiac resuscitation was performed. Ten patients presenting in cardiac arrest initially received resuscitative measures by emergency physicians according to Advanced Cardiac Life Support (ACLS) guidelines. A central venous catheter for fluid and drug administration and a femoral artery catheter for measurement of CPP (aortic minus right atrial relaxation phase pressures) were placed. When each patient was deemed nonsalvageable, 1.0 mg epinephrine was given and CPP was measured for 5 minutes, followed by a dose of vasopressin (1.0 U/kg). CPP measurements were continued for another 5 minutes. RESULTS: The mean duration of cardiac arrest (out-of-hospital interval plus duration of ED ACLS) was 39.6 +/- 16.5 min. There was no improvement in CPP after 1.0 mg of epinephrine. Vasopressin administration resulted in a significant increase of CPP in 4 of the 10 patients. Patients responding to vasopressin had a mean increase in CPP of 28.2 +/- 16.4 mm Hg (range: 10-51.5), with these peak increases occurring at 15 seconds to 4 minutes after administration. The increases in the vasopressin levels after administration did not differ between the responders and nonresponders. CONCLUSIONS: In this human model of prolonged cardiac arrest, 40% of the patients receiving vasopressin had a significant increase in CPP. This pilot study suggests that investigation of earlier use of vasopressin as a therapeutic alternative in the treatment of cardiac arrest is warranted.

Hemodynamic effects of aortic occlusion during hemorrhagic shock and cardiac arrest.

OBJECTIVE: To determine the hemodynamic consequences of aortic occlusion during controlled hemorrhagic arrest. METHODS: Ten anesthetized, hemodynamically monitored swine were subjected to a 40 mL/kg hemorrhage over 10 minutes, followed by a 5-minute period of apnea. At this time (T15), they were randomized into an UP group (n = 5) in which the thoracic aorta was occluded or a DOWN group (n = 5) in which the aorta was not occluded. Simultaneously, volume resuscitation with shed blood plus 20 mL/kg of normal saline was performed over a 10-minute period. Cardiac massage was performed until return of spontaneous circulation (ROSC), which was defined as a sustained systolic blood pressure > 60 mm Hg. After 30 minutes of occlusion (T45), the aortic occlusion was released. Parameters measured include mixed venous and arterial blood gases, serum lactic acid levels, cardiac index, mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), coronary perfusion pressure (CoPP), and left ventricular stroke work index (LVSWI). Oxygen delivery index (DO2I) was measured using a pulmonary artery catheter, and oxygen consumption index (VO2I) was measured by direct calorimetry (Delta Trac metabolic monitor). RESULTS: Four animals in each group achieved ROSC after 3.0 +/- 1.8 and 2.2 +/- 1.8 minutes in the occluded and nonoccluded groups, respectively. During cardiac compressions and volume resuscitation, the CoPP, MAP, and MPAP were greater in the UP group, although the differences did not achieve statistical significance. After volume resuscitation was complete and during the period of aortic occlusion (T25-T45), the UP group had significantly greater MAP (mm Hg), with a difference of 42.5 +/- 20.75 mm Hg at T25 and 44.7 +/- 19 mm Hg at T35 (p < 0.03). Despite no difference in DO2I, VO2I (mL/min/kg) was significantly lower in the UP group than in the DOWN group, 4.28 +/- 0.48 versus 8.33 +/- 0.85 at T25 (p = 0.0002) and 4.62 +/- 0.9 versus 7.09 +/- 0.72 at T35 (p = 0.0005). After release of aortic occlusion at T45, the UP group had significantly lower CoPP (mm Hg) than the DOWN group (20.5 +/- 17.3 versus 66.5 +/- 28.2 at T45, p = 0.03). LVSWI (g/kg) was also lower in the UP than in the DOWN group (18.6 +/- 8.28 versus 36.5 +/- 10.2 at T60 [p = 0.031 and 23.6 +/- 6.48 versus 48.8 +/- 15.3 at T240 [p = 0.021). After release of the occlusion, there were trends toward increased acidosis and lactic acid levels in the UP group. CONCLUSIONS: Aortic occlusion in this controlled hemorrhagic arrest model does not result in improved salvage but is associated with impaired left ventricular function, systemic oxygen utilization, and coronary perfusion pressure in the postresuscitation period.

Resuscitation of the critically ill in the ED: responses of blood pressure, heart rate, shock index, central venous oxygen saturation, and lactate.

To describe the simultaneous responses of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), heart rate (HR), shock index (SI = HR/SBP), central venous oxyhemoglobin saturation (ScvO2), and arterial blood lactate concentration (Lact) to resuscitation of critically ill patients in the emergency department (ED), an observational descriptive study was conducted in the ED of an urban teaching hospital. Thirty- six patients admitted from the ED to the medical intensive care unit were studied. Vital signs were measured immediately on arrival to the ED (phase 1). After initial resuscitation and stabilization, ie, HR between 50 and 120 beats/min and MAP between 70 and 110 mm Hg (phase 2), ScvO2 and Lact were measured and additional therapy was given in the ED to increase ScvO2 to > 65% and decrease Lact to < 2 mmol/L, if needed (phase 3). SBP, DBP, MAP, HR. SI, ScvO2, and Lact were measured. Initial resuscitation increased SBP from 103 +/- 39 to 118 +/- 29 mm Hg (P < .05) and MAP from 67 +/- 35 to 82 +/- 22 mm Hg (P < .05) but did not affect DBP (53 +/- 35 to 63 +/- 22 mm Hg, P = NS), HR (110 +/- 26 to 110 +/- 22 beats/min, P = NS) or SI (from 1.3 +/- 0.7 to 1.0 +/- 0.3, P =NS) from phase 1 to phase 2. ScvO2 remained < 65% and/or Lact > 2.0 mmol/L in 31 of 36 patients at phase 2, and additional therapy was required. Lact was decreased (from 4.6 +/- 3.8 to 2.6 +/- 2.5 mmol/L, P < .05) and ScvO2 was increased (from 52 +/- 18 to 65 +/- 13%, P < .05) without significant additional changes in SBP, DBP, MAP, HR, or SI at phase 3. The in-hospital mortality was 14% for this group of patients. It was concluded that additional therapy is required in the majority of critically ill patients to restore adequate systemic oxygenation after initial resuscitation and hemodynamic stabilization in the ED. Additional therapy to increase ScvO2 and decrease Lact may not produce substantial responses in SBP, DBP, MAP, HR, and SI. The measurement of ScvO2 and Lact can be utilized to guide this phase of additional therapy in the ED.

A technique revisited: hemodynamic comparison of closed- and open-chest cardiac massage during human cardiopulmonary resuscitation.

OBJECTIVE: To compare the hemodynamics of closed-chest cardiac massage vs. open-chest cardiac massage in patients resuscitated from cardiac arrest that occurred outside of the hospital. DESIGN: Prospective, non-outcome, case series. SETTING: Large urban emergency department. PATIENTS: Ten adult, normothermic, nontraumatic, out-of-hospital, cardiac arrest patients who failed advanced cardiac life support (ACLS) therapy. INTERVENTIONS: Patients presenting to the hospital in cardiac arrest were managed according to the ACLS protocol at the clinician's discretion. Proximal aortic and central venous pressure catheters were placed to measure arteriovenous compression- and relaxation-phase pressure gradients. After 5 mins of baseline measurements during closed-chest cardiac massage, patients underwent a left lateral thoracotomy, and open-chest cardiac massage was performed for 5 mins. MEASUREMENTS AND MAIN RESULTS: The mean coronary perfusion pressure and compression-phase pressure gradients were 7.3 +/- 5.7 and 6.2 +/- 5.4 mm Hg, respectively, during closed-chest cardiac massage, while increasing to 32.6 +/- 17.8 and 32.6 +/- 29.9 mm Hg, respectively, during open-chest cardiac massage. The differences between both measurements were statistically significant (p < .05). CONCLUSIONS: Open-chest cardiac massage is superior to closed-chest cardiac massage in providing relaxation-phase and compression-phase pressure gradients during cardiac arrest in patients failing current ACLS protocols. During open-chest cardiac massage, all patients exceeded the minimum coronary perfusion pressure of 15 mm Hg, which is recommended to obtain a return of spontaneous circulation. Further outcome studies are needed to determine the timeliness and appropriate indications for open-chest cardiac massage.

The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period.

BACKGROUND: Studies evaluating the dose of epinephrine required to optimize return of spontaneous circulation and survival after CPR have shown that doses greater than recommended by advanced cardiac life support (ACLS) improve coronary perfusion pressure and short-term resuscitation rates. Since survival has not improved, it is possible that higher doses of epinephrine may be physiologically detrimental in the postresuscitation period. OBJECTIVE: The object of this study is to measure the effect of the total cumulative dose of epinephrine given during ACLS on the hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. DESIGN: A prospective nonrandomized control trial of inception cohorts. SETTING: A large urban emergency department and intensive care unit. PATIENTS: Forty-nine successfully resuscitated witnessed, normothermic, nontraumatic, out-of-hospital patients, who had suffered cardiac arrests. INTERVENTIONS: All patients were treated according to ACLS guidelines; however, the epinephrine dose (0.01 to 0.2 mg/kg or 1 to 14 mg) was selected at the clinician's discretion and given through central venous access every 3 to 5 min. Hemodynamic, oxygen transport, and utilization variables were measured on a return of spontaneous circulation, and at least every 30 min thereafter under a standardized postresuscitation protocol. MAIN OUTCOME MEASURES: Hemodynamic, oxygen transport/utilization variables, and mortality in patients resuscitated from cardiac arrest. The total cumulative dose of epinephrine given during ACLS until a return of spontaneous circulation was recorded. RESULTS: A total cumulative epinephrine dose of 15 mg was found to best predict 24-h mortality. Of the 49 patients, 20 received less than 15 mg (group 1) and 29 received greater than 15 mg (group 2). Age, premorbid health status, sex, presenting rhythm, and duration of cardiac arrest were similar in both groups. The 24-h survival was 17 of 20 (85%) and 12 of 29 (41%) in group 1 and 2, respectively (p < 0.002). Over the first 6 h of the postresuscitation period, both groups had similar mean arterial pressure (MAP), mixed venous oxygen saturation, and systemic oxygen extraction ratio (all p > 0.1). Group 2, however, had a significantly lower cardiac index (CI), systemic oxygen consumption (VO2), and systemic oxygen delivery (DO2) (all p < 0.01). Systemic vascular resistance index (SVRI), initial and 6-h lactic acid levels were significantly higher in group 2 (all p < 0.03). CONCLUSIONS: The administration of all doses of epinephrine during the resuscitation of out-of-hospital cardiac arrest is associated with impairment of DO2 and VO2 in the postresuscitation period. Both duration and severity of these impairments correlate with the total cumulative epinephrine dose given during the resuscitation. Thus, inadvertent catecholamine toxicity represents a further complicating factor in the production of postresuscitation disease. Diagnostic and therapeutic interventions addressed toward mitigating these potentially reversible adverse effects may impact morbidity and mortality in out-of-hospital cardiac arrests.

Hemodynamics of interposed abdominal compression during human cardiopulmonary resuscitation.

OBJECTIVE: Clinical studies of interposed abdominal compression CPR (IAC-CPR) have had diverse outcomes. This study compared the hemodynamics of standard CPR and IAC-CPR in humans. METHODS: A 24-month prospective nonrandomized analysis of hemodynamic parameters was performed in a convenience cohort of 20 adults who had out-of-hospital, nontraumatic, normothermic cardiac arrests. The study took place in the resuscitation unit of a large urban hospital. Thoracic aortic and right atrial catheters were inserted and pressures were recorded during standard CPR and IAC-CPR. Coronary perfusion pressures (CPPs) were determined during standard CPR and IAC-CPR. The patients were separated into two groups based upon their responses to IAC-CPR. Responders had increases in CPP during IAC-CPR; nonresponders had decreases or no change in CPP during IAC-CPR. Aortic relaxation, right atrial relaxation, aortic compression, and right atrial compression phase pressures were compared between the two groups. RESULTS: CPPs increased in 13 patients and decreased in seven patients. The mean change in CPP with IAC-CPR was an increase of 5.8 +/- 15.1 torr. An elevated right atrial compression phase pressure (RaComp) during standard CPR was predictive of an increase in CPP during IAC-CPR (p = 0.047). In those patients who showed improvements in CPP during IAC-CPR, mean aortic relaxation phase pressures (AoRelax) increased by 9.5 +/- 14.2 torr (p = 0.026) and mean right atrial relaxation phase pressures (RaRelax) decreased by 2.6 +/- 6.2 torr (p = 0.099) during IAC-CPR. CONCLUSIONS: The variable effects of IAC-CPR on CPP appear to be multifactorial. The improvement in CPP that occurred in responders to IAC-CPR was secondary to an increase in AoRelax as well as a decrease in RaRelax.

Biphasic extrathoracic pressure CPR. A human pilot study.

HYPOTHESIS: Alternating intrathoracic pressure by means of a chest cuirass can cause perfusion and ventilation equal to or better than standard cardiopulmonary resuscitation (CPR) for humans in cardiac arrest. DESIGN: Nonrandomized, nonblinded, crossover pilot study. SETTING: Large urban emergency department. SUBJECTS: Five adult normothermic, nontraumatic, out-of-hospital cardiac arrest patients unresponsive to standard advanced cardiac life support. METHOD: Right atrial and aortic catheters were inserted for pressure measurement and blood gas analysis while the patient was receiving standard CPR by a pneumatic compression device (Thumper). The Thumper was then replaced by a chest cuirass (Hayek Oscillator). Pressure and blood gas measurements were then repeated. RESULTS: The coronary perfusion pressure increased from -1.2 +/- 8.6 mm Hg to 6.2 +/- 6.9 mm Hg for a mean change of 7.4 +/- 3.1 mm Hg (p = 0.006). The compression phase gradient increased 10.0 +/- 21.9 mm Hg (p = 0.364). The venous to arterial PCO2 gradient decreased 44.5 +/- 32.3 mm Hg (p = 0.070). The oxygen extraction ratio increased 1.6 +/- 9.4 percent (p = 0.761). The mean arterial PO2 and PCO2 changed from 252 to 240 mm Hg (p = 0.836) and from 53 to 66 (p = 0.172) mm Hg, respectively. CONCLUSION: The Hayek Oscillator chest cuirass produced a significant improvement in the coronary perfusion pressure. There was a trend for improved systemic perfusion as indicated by an improved compression phase gradient and venous to arterial PCO2 gradient, although this was not supported by the lack of improvement in the oxygen extraction ratio. The cuirass also adequately oxygenates and ventilates unassisted by positive pressure ventilation.

A characterization of hypothalamic-pituitary-adrenal axis function during and after human cardiac arrest.

OBJECTIVE: This study characterizes hypothalamic-pituitary-adrenal axis function during cardiopulmonary arrest and after return of spontaneous circulation. DESIGN: Prospective case series. SETTING: A large urban emergency department and intensive care unit over an 8-month period. PATIENTS: Two hundred five adult patients presenting in cardiopulmonary arrest to an urban emergency department. Three patients known to be taking corticosteroids were excluded from the study. MEASUREMENTS AND MAIN RESULTS: Cortisol concentrations were measured before and after advanced cardiac life support and for five consecutive hours after return of spontaneous circulation. Adrenocorticotropic hormone (ACTH) concentrations were measured before advanced cardiac life support and when the cosyntropin stimulation tests were performed 6 and 24 hrs after the return of spontaneous circulation. The mean initial serum cortisol concentration was 32.0 +/- 33.1 micrograms/dL (882.9 +/- 913.2 nmol/L). Fifty-three percent of patients had cortisol concentrations of < 20 micrograms/dL (< 552 nmol/L) at the end of cardiac arrest. Among 44 patients who achieved return of spontaneous circulation, 98% had initial cortisol concentrations of > 10 micrograms/dL (> 276 nmol/L) and 73% of patients had initial cortisol concentrations of > 20 micrograms/dL (> 552 nmol/L). Mean serum cortisol concentrations increased significantly (p = .0001) from 1 to 6 hrs after return of spontaneous circulation and decreased significantly (p = .03) from 6 to 24 hrs. A serum cortisol concentration of < 30 micrograms/dL (< 828 nmol/L) was associated with a 96% and 100% mortality rate at 6 and 24 hrs, respectively. Mean ACTH concentrations were increased without a significant difference between the initial and 6-hr concentrations. Mean ACTH concentrations decreased between 6 and 24 hrs (p = .06). There were no significant responses to the cosyntropin stimulation at 6 and 24 hrs. CONCLUSIONS: Cortisol concentrations after out-of-hospital cardiac arrest are lower than those concentrations reported in other stress states. There is an association between cortisol concentrations and short-term survival after cardiac arrest. Survivors have a significantly greater increase in serum cortisol concentrations than nonsurvivors during the first 24 hrs. Lower than expected cortisol concentrations for the extreme stress of cardiac arrest may have pathologic significance in the hemodynamic instability seen after return of spontaneous circulation. The etiology of the low cortisol concentrations may be primary adrenal dysfunction.

Measurement of oxygen consumption after uncomplicated acute myocardial infarction.

BACKGROUND: Oxygen consumption (VO2) has been shown to be decreased after acute myocardial infarction (AMI) complicated by cardiogenic shock. STUDY OBJECTIVE: To evaluate early measurement of VO2 by indirect calorimetry after an uncomplicated AMI (UAMI). STUDY DESIGN: Prospective nonrandomized case study. SETTING: Emergency department of a large urban hospital. PARTICIPANTS AND INTERVENTIONS: Twenty-six consecutive patients presenting with confirmed UAMI. VO2 was measured by indirect calorimetry (Deletrac, Datex Ins,) which is noninvasive. All patients received buccal or intravenous nitroglycerin and thrombolytic therapy, and none received opiates before VO2 measurement. RESULTS: Two groups of patients were identified by subsequent development of cardiogenic shock. Group 1 did not develop cardiogenic shock, and group 2 developed shock within 24 h of admission. Group 1 (n = 22) had a significantly higher VO2 compared to group 2 (n = 4), mean 154(SD 25) vs mean 100(SD 13) ml/min.m2, p < 0.002. Group 1 had a significantly higher increase in basal metabolic rate than group 2, mean 30 percent (SD 11) vs mean 10(SD 15) percent, p < 0.007. There was no significant difference in age, heart rate (HR), shock index (SI), or rate-pressure product (RPP) between groups 1 and 2. All patients in group 2 developed cardiogenic shock despite thrombolytic therapy, and two died within 24 h of admission. CONCLUSION: VO2 is increased in UAMI and represents increased metabolic demands of peripheral tissues and not cardiac oxygen uptake. A reduction in VO2 (< 100 ml/min.m2) after AMI may be an early predictor of subsequent development of cardiogenic shock. Measurement of VO2 in UAMI by indirect calorimetry in the emergency department may be of value to identify patients at high risk and could influence their management.

Simultaneous radial, femoral, and aortic arterial pressures during human cardiopulmonary resuscitation.

OBJECTIVE: To examine the validity of interchanging arterial sites and their responses to graded doses of epinephrine during human cardiopulmonary resuscitation (CPR). DESIGN: Consecutive case series. SETTING: Large, urban Emergency Department. PATIENTS: Adult, normothermic, nonhemorrhagic cardiac arrest patients. INTERVENTIONS: While receiving advanced cardiac life support, patients received right atrial (n = 40), aortic (n = 40), radial (n = 40), and femoral (n = 17) artery catheters. Pressures were measured simultaneously at baseline, after 0.01 mg/kg and 0.2 mg/kg of epinephrine. MEASUREMENTS AND MAIN RESULTS: The mean aortic compression-phase pressure was 9.3 +/- 10 (SD), 8.1 +/- 11, and 4.4 +/- 9.5 mm Hg higher than radial artery pressure at baseline, after 0.01 mg/kg, and 0.2 mg/kg of epinephrine, respectively (all statistically significant). When compared with the femoral artery at the same time points, the mean aortic compression-phase pressure was also 3.0 +/- 6.8, 1.9 +/- 8, and 0.6 +/- 7.7 mm Hg higher, respectively (none statistically significant). The aortic relaxation-phase pressure was 1.3 +/- 3.6, 1.1 +/- 3.8, and 1.6 +/- 2.5 mm Hg lower than the radial artery at baseline, after 0.01 mg/kg and 0.2 mg/kg of epinephrine, respectively (all statistically significant). When compared with the femoral artery at the same time points, the aortic relaxation-phase pressure was 0.6 +/- 2.0, 0.3 +/- 3.3, and 0.3 +/- 2.4 mm Hg lower, respectively (none statistically significant). CONCLUSIONS: Radial artery relaxation-phase pressure, although statistically higher, correlated with aortic relaxation-phase pressure. Femoral artery relaxation-phase pressure was not statistically different from aortic relaxation-phase pressure. Aortic pressure was statistically higher and had a lower correlation with radial artery pressures during compression phase. The aortic to radial artery and aortic to femoral artery compression-phase gradients abated with increasing doses of epinephrine therapy. Caution must be used when substituting compression-phase pressure obtained at radial or femoral artery sites for aortic pressure during human CPR. Coronary artery perfusion pressures obtained with radial and femoral arteries correlate with aortic pressure when measuring the response to vasopressor therapy during CPR when an interpretable waveform exists.

Functional responses to extremely high plasma epinephrine concentrations in cardiac arrest.

OBJECTIVE: To evaluate the action of high-dose epinephrine by measuring simultaneously its vasopressor and norepinephrine releasing effects in humans during cardiac arrest. DESIGN: A prospective study on consecutive patients admitted with cardiac arrest. SETTING: Emergency Department in a large, urban hospital. PATIENTS: Eighteen patients with out-of-hospital cardiac arrest undergoing cardiopulmonary resuscitation (CPR). INTERVENTIONS: Catheterization of both the aorta and right atrium for the recording of pressure and collection of blood samples. Throughout the study period (12.5 mins), 18 patients received epinephrine at both the standard dose (1 mg, approximately 0.015 mg/kg) and high dose (0.2 mg/kg). Blood samples were drawn five times, every 2.5 mins. MEASUREMENTS AND MAIN RESULTS: Plasma epinephrine and norepinephrine concentrations; aorta, right atrial, and coronary perfusion pressures. Epinephrine concentrations (normal at rest = 160 +/- 10 [SEM] pmol/L) were increased at the time of the first sample (2.5 mins) by approximately 3,000-fold (to approximately 0.5 mumol/L), and, increased further to 12,000-fold (approximately 2.0 mumol/L) during the study. Aortic pressure increased from 20 +/- 3 to 28 +/- 3 mm Hg (p < .001), and coronary perfusion pressure increased from 4 +/- 3 to 10 +/- 3 mm Hg (p < .001). Simultaneous plasma norepinephrine concentrations were 30-fold higher than the normal resting value of 1.30 +/- 0.04 nmol/L, and increased by 90-fold during the study (p < .001). The spectral distributions of the individual correlations between plasma epinephrine and norepinephrine concentrations were segregated into high correlations (r > .83) in 12 of 18 patients and low r values (r = .29 to .79) in the remaining six patients. The distribution of the correlations was nonuniform by the Kolmogorov-Smirnov goodness-of-fit test with p < .001; this profile suggests that norepinephrine responsiveness to epinephrine can separate two populations, one of which (r > .83) would have preserved viability of the corresponding epinephrine receptors. The correlations between plasma epinephrine concentrations and coronary perfusion pressures were distributed more evenly, also in a nonuniform pattern (p < .02 by Kolmogorov-Smirnov goodness-of-fit test) and the relationship between the two sets of correlations was not significant. CONCLUSIONS: Despite the very high prevailing plasma epinephrine concentrations during cardiac arrest, further epinephrine increases still elicit biological responses. The present work provides physiologic support for the use of large doses of epinephrine during the course of CPR.