Postarrest Targeted Temperature Management Immediately Following Craniotomy

Abstract

Therapeutic hypothermia or targeted temperature management (TTM) has been shown to improve survival and neurological outcome after cardiac arrest. TTM is not frequently utilized in the postoperative setting because of the concern for exacerbation of bleeding. We present the case of a 65-year-old man who had a cardiac arrest during craniotomy for a brain tumor resection. He was successfully resuscitated from pulseless electrical activity and remained unresponsive. After assessment for postoperative brain hemorrhage, the neurocritical care team initiated TTM. Repeat imaging revealed no additional bleeding. The patient was discharged with a cerebral performance category of 1 to an acute rehabilitation center 11 days following his cardiac arrest. This case highlights the need for further consideration of TTM in the postoperative cardiac arrest population.

Background

Targeted temperature management (TTM) has been shown to improve survival and neurological outcome in survivors of cardiac arrest (Bernard et al., 2002; Hypothermia after Cardiac Arrest Study Group, 2002; Sagalyn et al., 2009; Kim et al., 2012). Postoperative cardiac arrest (CA) patients have been excluded from TTM studies and TTM clinical care protocols over concerns that TTM might exacerbate postoperative bleeding (Polderman, 2009). While many TTM protocols currently in use exclude CA patients following surgery, major trauma, or with major hemorrhage, others include patients in the postoperative phase, provided that hemorrhage was not the direct source of the CA (Center for Resuscitation Science, 2013). Although the benefits of TTM following postoperative CA remain unclear, it is increasingly recognized that cooling should be a consideration for the majority of patients after CA, even in the setting of recent surgical intervention (Abella, 2011; Rinehart et al., 2012). This case report describes a patient who was successfully treated with TTM after a pulseless electrical activity (PEA) arrest immediately following craniotomy, without radiographic or clinical evidence of bleeding complications. This case therefore provides proof of concept that postarrest TTM may be employed safely for select patients following operative intervention.

Case Presentation

A 65-year-old man with a history of hypertension and type II diabetes was admitted to our hospital for surgical resection of a recurrent pituitary mass. A right frontotemporal pterional craniotomy was performed; the sylvan fissure was opened, and the cerebral arteries and optic chiasm were identified. The tumor capsule was found to be adherent to the circle of Willis and arachnoid planes. It was decided that tumor decompression was associated with unacceptable risk, and the resection was terminated. The dura was closed and bone flap secured. Following suturing of the temporalis fascia, a subgaleal drain was placed, and the skin was closed with staples. Estimated blood loss was 200 mL. Upon emergence from anesthesia, the patient was following commands and was extubated in the operating room.

Immediately following transport to the neurological intensive care unit, the patient had a generalized tonic–clonic seizure. Hemoglobin saturation fell to 50%. The patient was oxygenated with 100% oxygen and was ventilated with a bag/valve mask. Blood pressure, measured by an arterial catheter, decreased to 60/15 mmHg, and the heart rate became irregular at 50–60 beats per minute. The patient subsequently became apneic and cyanotic, and experienced a PEA CA. Cardiopulmonary resuscitation (CPR) was initiated and 1 mg of epinephrine was given. After approximately 3 minutes, return of spontaneous circulation (ROSC) with sinus tachycardia was achieved, accompanied by an acute hypertensive episode treated with nicardipine. Levetiracetam and phenytoin were administered for seizure prophylaxis, and continuous electroencephalogram (cEEG) monitoring was initiated. Following administration of rocuronium and propofol, the patient was intubated. Portable computerized tomography of the brain (CT) revealed no new intraparenchymal hemorrhage. However, there was a small right-sided subdural hematoma and cerebral edema.

The neurocritical care team weaned the propofol 4 hours later to reassess the patient's neurological exam, and the patient again suffered a clinical seizure. Repeat brain CT revealed no acute infarction, shift, or hemorrhage. Only stable postsurgical changes were seen—extra-axial blood products and scattered foci of pneumocephalus—unchanged from the previous CT 4 hours. Six hours following the CA, the patient remained unresponsive. The neurosurgical and neurocritical care teams elected to initiate postresuscitative TTM, cognizant that the patient's neurologic exam may have been limited by a post-ictal state, and acknowledging that TTM had not been studied in patients with in-hospital arrest in the setting of both seizure and recent neurosurgery. Prior to initiation of TTM, a right internal jugular catheter was inserted which allowed continuous central venous oxygenation and central venous pressure monitoring; a radial arterial line had been placed prior to surgery. A rectal probe provided thermoregulatory feedback to a surface cooling device (Arctic Sun, Bard Medical, Covington, GA), programmed to induce and maintain hypothermia at 33°C. Propofol was continued for sedation.

Initial serum laboratory values were unremarkable with the exception of a modestly elevated creatinine (1.66 mg/dL). Electrocardiographic findings did not reveal evidence of acute ischemia. Prior to cooling, at a temperature of 35.5°C, hemoglobin was 11.6 g/dL, platelet count was 240 thousand/uL, activated partial thromboplastin time (aPTT) was 27.5 seconds, international normalized ratio (INR) was 1.2, and fibrinogen was 367 mg/dL. Two and a half hours after TTM initiation, the patient's temperature rose to 36.5°C. Intravenous neuromuscular blockade was begun, and 1 L of cold (4°C) normal saline was rapidly infused. Target temperature (33°C) was attained within 1 hour after these measures, and was maintained for 24 hours. The patient manifested typical side effects of TTM (asymptomatic bradycardia, initially increased urine output and hypokalemia). In addition, the TTM maintenance phase was remarkable for several episodes of hypotension responding to 500–1000 mL boluses of normal saline with brief episodes of vasopressor support. The postarrest TTM rewarming phase, proceeding over 12 hours, was uneventful with the exception of an episode of shivering alleviated with intravenous meperidine.

Following rewarming, the patient experienced confusion and nocturnal agitation but achieved a Glasgow Coma Scale of 15 by day three post rewarming. The seizures did not recur, and the patient received treatment for persistent panhypopituitarism with levothyroxine, DDAVP, and hydrocortisone. Eleven days following CA, he was discharged to an acute rehabilitation center with a Cerebral Performance Category 1 functional status.

During this patient's TTM course, there was no evidence of clinically significant bleeding. The subgaleal drain exhibited only trivial output and was removed upon completion of patient rewarming. The craniotomy incision was consistently clean and dry. After the patient's initial seizure prior to the CA, cEEG monitoring displayed only a single episode of burst suppression while the patient was being cooled. Gadolinium-enhanced magnetic resonance imaging (MRI) was performed 4 hours after the patient was rewarmed to normothermia. The study confirmed the presence of right frontal/temporal scalp swelling, parenchymal swelling, and minimal extra-axial fluid underlying the craniotomy, as seen in the brain CT performed immediately prior to cooling. No new infarction, midline shift, or acute parenchymal or subarachnoid hemorrhage was visualized (see Fig. 1). A repeat MRI 1 month after discharge was unchanged. Coagulation parameters and hemoglobin were closely monitored during and after the course of hypothermia. Fibrinogen levels peaked coincident to the platelet nadir at 31 hours after induction of TTM; platelet count subsequently improved. The aPTT and prothrombin times varied minimally. See Table 1 for temperature/time-correlated laboratory values.

FIG. 1.

Imaging of the brain preoperatively (prior to cooling) and four hours following rewarming. (A) Magnetic resonance imaging (T1 sequence) 1 week prior to operative intervention. (B) Magnetic resonance imaging (T1 sequence) following rewarming (68 hours following arrest) showing surgical changes with typical mild FLAIR hyperintensity and swelling but without any evidence of new intraparenchymal or subarachnoid hemorrhage.

Table 1.

Time/Event/Temperature-Related Laboratory Values

Time/event	Temperature (°C)	Hemoglobin (g/dL)	Platelets (k/uL)	aPTT (sec)	INR
Hour
0—Cardiac arrest	36.7	14.1	311	23	1.2
6—TTM initiated	36.5	11.6	240	27.5	1.2
12	32.4	12.0	231	26.9	1.2
24	33.0	11.1	232	27.3	1.2
34—Rewarming initiated	32.7
48	36.8	11.5	198	27	1.1
64—Normothermia	37.1	10	181
Day
4	37.2	10.5	184
7	36.8	12.6	238	25.2	1.2

All available hemoglobin and coagulation values within the first 3 days are labeled±1 hour of actual laboratory report.

Discussion

This case represents a clinical scenario in which most providers might opt to withhold postarrest TTM. The patient suffered an in-hospital PEA CA immediately following a highly invasive neurosurgical procedure and seizure. To our knowledge, this is the first report of successful TTM in a patient immediately following brain surgery. In this case, there was clear radiographic evidence suggesting no exacerbation of postoperative bleeding secondary to TTM. While it remains unclear whether all such postoperative patients can be cooled successfully, this case illustrates that selected postoperative patients may undergo TTM safely.

More generally, this case illustrates the complex issue of TTM following in-hospital CA. The evidence in support of TTM for in-hospital CA derives largely from cohort studies comparing outcomes in historical controls (pre-TTM use at a given study site) to patient cohorts treated with mild therapeutic hypothermia (Holzer et al., 2006; Kilgannon et al., 2012). CA in the in-hospital setting most often presents as a non-shockable rhythm. In approximately 75% of these arrests, the initial rhythm is PEA or asystole (Brady et al., 2011). Although there are no randomized studies of postarrest TTM for patients with non-shockable rhythms, multiple investigations have suggested improved survival with TTM use regardless of initial rhythm (Oddo et al., 2006; Arrich et al., 2007; Gaieski et al., 2009).

Of particular concern in this patient was the potential for bleeding related to recent neurosurgery. A generally held principle regarding TTM use is that reduction in core body temperature precipitates a multifactorial coagulopathy, platelet dysfunction, and prolongation of the partial thromboplastin time (Valeri et al., 1995; Watts et al., 1998; Polderman and Herold, 2009). Recent preclinical evidence in trauma models suggests that mild hypothermia can be safely carried out after hemorrhage is controlled and hemodynamic stabilization is achieved with fluid resuscitation (Mohr et al., 2013). A limited number of case series and publications have evaluated TTM for in-hospital arrest after trauma or surgical procedures (Tuma et al., 2011; McGrane et al., 2012; Rinehart et al., 2012). No patient exhibited significant coagulopathy or bleeding complications (Table 2). Literature specific to the safety of non-CA TTM in patients undergoing craniotomy is inconclusive (Clifton, Allen, et al., 1992; Clifton, Coffey, et al., 2012; Todd et al., 2005; Georgiou and Manara, 2013). These studies represent limited patient populations who undergo TTM of variable depth and duration to treat brain injury and aneurysm. Intracranial bleeding does not appear to be a significant risk factor.

Table 2.

Summary of Recent Literature Pertaining to Post-arrest TTM Following Surgical Procedure or Trauma

Year	Study	Type of study	Patient type	Cohort size	Target temperature	Bleeding	Outcomes
2012	Rinehart et al.	Case series	Postoperative cardiac surgery	3 patients	33–35°C	None	2 patients CPC 1; 1 patient CPC 3
2011	Tuma et al.	Case series	Acute trauma	6 patients	32–34°C	None	2 patients GCS 15; 1 patient GCS 14; 2 patients GCS 11t; 1 patient death
2012	McGrane et al.	Case report	In-hospital exsanguination	1 patient	34–35°C	None reported	Successful neurological and functional outcome

CPC, Cerebral Performance Category; t, tracheostomy; GCS, Glasgow Coma Scale.

In this report of a patient with postoperative PEA arrest, TTM likely promoted a favorable neurological outcome and was not associated with additional postoperative intracerebral bleeding. This case report suggests that TTM may be safe and effective in this population, although evaluation of the risk–benefit ratio for TTM use must be made on a case-by-case basis. Rapid recognition and treatment of the hypoxic emergency, immediate and effective cardiopulmonary resuscitation, and appropriate advanced cardiac life support effectively treated this patient's initial ischemic event. Systematic evaluation of the continued presence of coma culminated in the decision to initiate TTM. Further investigation into the use of TTM for postoperative patients is required, as this represents an important subset of in-hospital CA.

Footnotes

Author Disclosure Statement

Dr. Abella: Stryker, Medivance Corp–honoraria, HeartSine–consultant/advisory board, Resuscor–modest ownership, Stryker, NHLBI, Philips, Medtronic, Doris Duke–significant research grants; Ms. Leary: Stryker, Philips–honoraria.

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Postarrest Targeted Temperature Management Immediately Following Craniotomy—A Case Report