Ben-David, Bruce MD*,; Stonebraker, Vincent C. MD*,; Hershman, Robin CRNA*,; Frost, Christopher L. CRNA*,; Williams, H. Kenneth MD†
Departments of *Anesthesiology and †Surgery, Allegheny General Hospital, Pittsburgh, Pennsylvania
November 11, 2000.
Address correspondence and reprint requests to Bruce Ben-David, MD, Department of Anesthesiology, Allegheny General Hospital, 320 East North Ave., Pittsburgh, PA 15212. Address e-mail to firstname.lastname@example.org.
IMPLICATIONS: A patient having emergency repair of a ruptured abdominal aortic aneurysm experienced an intraoperative cardiac arrest and was unsuccessfully resuscitated. Ten minutes after termination of cardiopulmonary resuscitation, the patient had a spontaneous return of circulation and a complete physical and neurologic recovery.
Since the earliest reports in 1982 (1,2), there have been more than 24 reported cases of survival after failed resuscitation (3,4). This phenomenon has been variously referred to as “spontaneous return of circulation” (SROC) or “Lazarus syndrome”(5). Of these cases, at least eight patients have survived neurologically intact. We report of such a case, and discuss its potential mechanisms and implications
A 66-yr-old man, weighing 80 kg, was emergently brought to the operating room (OR) with a suspected leaking abdominal aortic aneurysm. His past history included hypertension and a transient ischemic attack 4 yr earlier. He also had a 50-pack/yr smoking history and chronic renal insufficiency (creatinine 2.3 mg/dL). He had no history of metabolic disorder. He had received 2600 mL of lactated Ringer’s solution before arrival in the OR. Vital signs on arrival included a heart rate of 120 bpm and a systolic blood pressure of 60 mm Hg. The patient was pale, mottled, diaphoretic, and tachypneic. Rapid administration of warmed IV fluids via two rapid infusion systems increased his systolic blood pressure to 120 mm Hg.
Induction of anesthesia proceeded uneventfully with d-tubocurarine 3 mg, fentanyl 250 μg, etomidate 20 mg, and succinylcholine 160 mg IV before rapid sequence endotracheal intubation. Maintenance of anesthesia included inhalation of isoflurane (as tolerated by blood pressure) in 100% oxygen. Pancuronium 6 mg was given for continued neuromuscular blockade. With induction of anesthesia, the vital signs remained stable (systolic blood pressure 110–120 mm Hg by automated cuff pressure) and surgical incision promptly followed at 0533. An arterial blood gas drawn at this time revealed hemoglobin 8.1 g/dL, K+ 3.8 mEq/L, glucose 185 mg/dL, pHa 7.24, Paco2 41 mm Hg, Pao2 479 mm Hg, HCO3 16 mEq/L, and base excess −10.6 mEq/L. At this time, the end-tidal CO2 was 29 mm Hg. Electrocardiogram (EKG) showed a cardiac rhythm of sinus tachycardia.
At 0548, the surgeon placed a cross-clamp across the suprarenal aorta. This led to an increase in systolic pressure to 160 mm Hg, but no apparent changes on the EKG. At 0553, the clamp was shifted to an infrarenal position. At 0559, the cardiac rhythm suddenly deteriorated into ventricular tachycardia, which rapidly progressed to ventricular fibrillation. Chest compressions were initiated, and the patient was ventilated with 100% oxygen. This resuscitation continued for the next 17 min during which time the patient received a total of nine countershocks of 360 J each. Additionally, a total of 5 mg of epinephrine, 4 mg of atropine, 2 g of CaCl2, 400 mg of lidocaine, 150 mEq of NaHCO3 and 2 g of MgSO4 were given IV. Chest compressions were initially thought to be effective as the end-tidal CO2 was maintained at 25–32 mm Hg. No arterial line was yet available to observe a waveform or to draw blood gases, and no single-stick arterial blood gas was drawn during the resuscitation. Despite the resuscitation efforts, the underlying rhythm continued to be asystole. This was confirmed by the palpation of a flaccid and pulseless (in the absence of chest compressions) proximal aorta. End-tidal CO2 had diminished to 8–10 mm Hg, and the pupils were widely dilated. Because of the patient’s complete lack of response and the apparent deterioration by end-tidal CO2, the attending surgeon and anesthesiologist mutually agreed to discontinue the resuscitation. The patient was pronounced dead at 0617.
With cessation of the resuscitation, the IV medications and infusions were discontinued. The monitors were turned off, and the ventilator was disconnected although the endotracheal tube was left in situ. The surgeon stayed at the operating table, using the opportunity to teach residents and students. At 0627, 10 min after the pronounced death of the patient, the surgeon announced that he had begun to feel a pulse in the proximal aorta above the level of the aortic cross-clamp. Ventilation with 100% oxygen was recommenced and revealed an end-tidal CO2 of 29 mm Hg. The EKG was reconnected and showed a sinus rhythm of 90 bpm. Systolic blood pressure was 90 mm Hg by automated cuff. A radial arterial line was now inserted successfully, and at 0630, arterial blood gases were: hemoglobin 9.5 mg/dL, K+ 3.5 mEq/L, glucose 323 mg/dL, pHa 7.17, Paco2 54.4 mm Hg, Pao2 438 mm Hg, and base excess −8.0 mEq/L. An esophageal temperature probe was inserted and measured 33.4°C. It was decided to proceed with the operation although neurologic prognosis was anticipated to be bleak. The patient was hemodynamically stable throughout the remainder of the procedure, requiring no inotropic support. Total fluid administration for the operation was 16 U of packed red blood cells, 8 U of fresh frozen plasma, 20 U of platelets, and 12 L of crystalloid solutions. Despite warming of all IV fluids and blood products and the use of a forced air warming blanket, the patient’s temperature ranged between 33° and 34°C for the remainder of the operation. The leaking aneurysm was resected uneventfully and the patient was transported to the intensive care unit.
Postoperatively, the patient was maintained on mechanical ventilation for several days in the intensive care unit. The postoperative course was complicated by mild renal insufficiency and two bouts of atrial arrhythmias (both of which were self-limiting). Remarkably, the patient improved dramatically and, after tracheal extubation, was found to be completely neurologically intact. He appeared to have no short- or long-term memory deficits. He also had no recall of any events of the day of operation except for being initially brought into the OR.
He was discharged home on postoperative Day 13 in excellent condition with no apparent neurologic deficit. Follow-up at 5 wk revealed that the patient had fully recovered, and had resumed full physical activities and his lifestyle of prior to the surgery.
Although only a handful of such cases have appeared in the literature, there has been speculation that the Lazarus phenomenon occurs more often than those few reports would suggest (5). Possible explanations for the reluctance to report these cases include: 1) a concern regarding medicolegal ramifications, 2) a fear of being criticized for negligence or hyperbole, 3) the lack of a satisfying physiologic explanation for the events, 4) the lack of complete documentation or monitoring of the event, and 5) the physician’s disbelief of his or her own observations.
Various mechanisms have been suggested as explanation for the phenomenon. Bradbury (6) suggested delayed delivery to the heart of previously administered adrenaline as the basis for SROC in a patient after acute myocardial infarction and left ventricular failure. Voelckel and Kroesen (7) reported a case of suspected hyperkalemic cardiac arrest, and hypothesized that SROC seven minutes after discontinuing the resuscitation was attributable to a gradual intracellular shift of potassium after previously administered bicarbonate. Quick and Bastani (8) attributed SROC eight minutes after declaration of death to a similar mechanism. One case report described SROC five minutes after discontinuation of cardiopulmonary resuscitation (CPR) intraoperatively during thoracoabdominal aortic endovascular stent-graft placement (9). The postulated mechanism in that case was a spontaneous dislodging of embolized endovascular plaque from the coronary artery, which then allowed cardiac reperfusion.
A few authors have discussed “auto-PEEP” as a possible mechanism to explain SROC (10–12). During CPR, dynamic hyperinflation may develop in a patient with obstructive airway disease because of hyperventilation and inadequate exhalation time. Cessation of ventilation relieves the hyperinflation and the excessive intrathoracic pressure, thus allowing cardiac filling and permitting the spontaneous return of cardiac function. Lapinsky and Leung (13) reviewed 89 cases of CPR of which 34 had documentation of electromechanical dissociation. In 16 of these 34 patients, there were autopsy or clinical findings that provided an explanation of the electromechanical dissociation. Thirteen of the remaining 18 patients (72%) had a history of obstructive airway disease in contrast to an incidence of 11% in the other patients who had been resuscitated.
Of these various mechanisms, that which seems most relevant in this case is that of positive pressure ventilation increasing intrathoracic pressure, which then impeded venous return. Hypovolemia would also have exaggerated the deleterious effect of intrathoracic pressure on venous return. With the cessation of positive pressure ventilation, perhaps enhanced passive filling of the quiescent heart stimulated spontaneous electrical activity. And perhaps this spontaneous rhythm went unnoticed for some minutes. Having been ventilated with 100% oxygen, there would have been an oxygen reserve in the residual capacity of the lungs that could have provided for oxygenation during this period of unrecognized SROC. Reduced oxygen consumption secondary to the hypothermia (which certainly also afforded significant neurologic protection), and the fact that arterial perfusion was limited to the level above the aortic clamp, might have also played a role. In addition, residual epinephrine from earlier injections may have been a sufficient vasopressor to sustain the blood pressure during this time. The large dose of epinephrine used could also explain the dilated pupils that may not, therefore, have reflected his neurologic status. It is also interesting to speculate on the possible role of the aortic cross clamping and the associated changes in preload, afterload, and humoral factors in causing the initial arrest, as well as how these factors might have changed both during and after the resuscitation to have allowed SROC.
One of the lessons relearned from this case is the original recommendation of Linko et al. (1) to continue monitoring for 10 minutes after discontinuation of CPR. That recommendation has been echoed by others, and this case adds further support for this practice. Such a case invariably raises the question whether CPR was terminated prematurely. Unfortunately, once one has run a full course of the relevant advanced cardiac life support algorithm, the decision as to when to cease resuscitation efforts remains a difficult one. There appears to be no consensus as to the appropriate timing or specific guidelines regarding the termination of CPR, a decision also likely to be influenced by the particulars of the individual case. Perhaps resuscitation efforts should be continued unless proven ineffective by end-tidal CO2 <10–15 mm Hg or evidence of metabolic deterioration (4,9,14,15). Ours is the only reported case of Lazarus syndrome that includes documentation of end-tidal CO2 monitoring. Before termination of resuscitation, the end-tidal CO2 values had been ≤10 mm Hg, so this would not have been an indication to persist. However, if hyperventilation or dynamic hyperinflation had been present, it would have depressed end-tidal CO2 to values that did not accurately reflect the metabolic state. Therefore, the recommendation regarding end-tidal CO2 values may not be relevant where factors beyond the hemodynamic one may also affect the end-tidal CO2.
A case of Lazarus syndrome, particularly with full neurologic recovery of the patient, is both disturbing and humbling. It is disturbing in that it casts doubt on one’s past decisions and infuses with uncertainty all future decisions as to appropriate cessation of unsuccessful CPR. And it is a humbling reminder to find that our efforts and judgements are not necessarily the final arbiters of outcome. Perhaps it is a supreme hubris on our part to presume that we can reliably distinguish the reversible from the irreversible, or the salvageable from the nonsalvageable. In a poignant irony, at exactly the time this case was progressing in the OR, our Department of Anesthesiology was holding its monthly meeting. The topic of discussion was a proposed hospital policy to allow “nonbeating heart” organ donation. This is a policy that allows for organ donation immediately after the death of a patient who does not meet strict brain-death criteria but whose family wishes to terminate life support (16). In this scenario, the patient is brought to the OR where life support is discontinued and, immediately after a declaration of death, the organ harvesting is begun. Given our demonstrated imperfect ability to absolutely determine irreversibility or a specific “time of death,” the above practice indeed seems problematic. We are not the first to draw an uneasy connection between cases of Lazarus syndrome and organ harvesting practices (17).
In conclusion, we present a case of spontaneous recovery after failed intraoperative CPR (Lazarus syndrome). We suggest that it may be worthwhile to give a brief trial of disconnecting ventilation when the patient is otherwise unresponsive to resuscitation efforts. We concur with previous authors who recommend continued monitoring for 10 minutes after cessation of CPR. And lastly, although a very low end-tidal CO2 has been suggested as an indicator of poor outcome during CPR, and thus as an indicator of when to terminate resuscitation, this may not always be so.
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