Therapeutic Hypothermia for Brain Injury from Near Hanging: Review of the Literature

Abstract

Hanging, strangulation, and suffocation constitute the second most common cause of death by suicide in the United States after firearms. Near hanging is defined as an unsuccessful attempt at hanging. Victims of near hanging suffer from strangulation with cerebral ischemia and resultant reperfusion injury, irrespective of whether they had cardiac arrest or not. The acute post-injury period is characterized by several pathophysiologic processes that start in the minutes to hours following injury. All of these processes are temperature dependent; they are all aggravated by fever and inhibited by hypothermia. In this article, we review the current clinical evidence on the use of therapeutic hypothermia (TH) for comatose near-hanging patients. We identified seven studies involving TH for near hanging on 51 patients. All the studies are retrospective reviews or case reports. TH (32–33°C) was applied for 24–36 hours. Even though some studies showed that near-hanging victims who present comatose to the hospital can have good neurologic outcomes after supportive therapy alone, some patients are still left with a poor neurologic outcome, especially if they sustained cardiac arrest. Prospective studies are warranted to test the potential benefit of TH on neurologic outcome and survival in this patient population. Although it would be difficult to conduct such studies, we feel that the compelling case studies, anecdotal evidence, and extrapolated data support its use until more evidence can be obtained.

Introduction

Hanging, strangulation, and suffocation constitute the second most common cause of death by suicide in the United States after firearms, accounting for 23.5% of 34,500 suicide-related deaths annually (US Census Bureau, 2012). There has been an increase in suicides by hanging during the last decades, and the victims are primarily young males (84%; Gunnell et al., 2005; Martin et al., 2005). About 22% of all hanging victims are transported to a hospital's emergency room (ER); the remaining 78% either are found dead or die after resuscitation attempts in the field (Aufderheide et al., 1994). For those who make it to the hospital, 14% die in the ER and 18% die after admission, with an overall mortality rate of 33% (Martin et al., 2005). Near hanging is defined as an unsuccessful attempt at hanging. The majority of near-hanging patients that make it to the ER are comatose. Victims of near hanging suffer from strangulation with cerebral ischemia and resultant reperfusion injury rather than a fatal cervical spine injury, irrespective of whether they had cardiac arrest or not. Studies show that near-hanging patients who suffer cardiac arrest, present with a Glasgow Coma Scale (GCS) of ≤5, and experience a longer hanging time have the worst prognosis (Matsuyama et al., 2004; Penney and Stewart, 2002). During a 10-year study period, four factors were found to be significantly associated with poor outcome: systolic blood pressure <90, a Glasgow coma score ≤8, anoxic brain injury on computed tomography (CT) scan, and an injury severity score >15. However, logistic regression analysis found only anoxia on a CT scan to be independently associated with poor outcome (Salim et al., 2006). In one retrospective analysis, 40% of near-hanging patients who presented without cardiac arrest and did not receive therapeutic hypothermia (TH) had poor neurologic outcome (Borgquist and Friberg, 2009). There is no specific treatment for comatose near-hanging patients beyond general supportive therapy in the intensive care unit (ICU).

The mechanism of injury to the brain in near hanging is due to ischemia–reperfusion injury similar to cardiac-arrest patients with return of spontaneous circulation. In ischemia–reperfusion injuries, the acute post-injury period is characterized by several pathophysiologic processes that start in the minutes to hours following injury and may last for hours to days. These result in further neuronal injury, and are termed the secondary injury. Cellular mechanisms of secondary injury include all of the following: apoptosis, mitochondrial dysfunction, excitotoxicity, disruption in ATP metabolism, disruption in calcium homeostasis, increase in inflammatory mediators and cells, free radical formation, DNA damage, blood–brain barrier disruption, brain glucose utilization disruption, microcirculatory dysfunction, and microvascular thrombosis. These mechanisms are described in detail elsewhere (Dietrich et al., 2009; Polderman, 2009). All of these processes are temperature dependent; they are all aggravated by fever and inhibited by hypothermia (Dietrich et al., 2009). Based on the current evidence that TH can be neuroprotective from ischemia–reperfusion injury, then applying TH to near-hanging victims could potentially improve outcomes in this patient population.

Methods

We queried the Medline database with the MeSH terms “Hypothermia, induced,” “Hypothermia, therapeutic,” “hypothermia,” “hanging,” near-hanging,” and “asphyxia” from 1993 to 2012. We utilized both PubMed and OVID to maximize database penetration. We searched the Cochrane Database of Systematic Reviews. We also hand searched bibliographies of relevant citations and reviews. Inclusion criteria were double-blind, placebo-controlled, randomized controlled trials (RCTs), observational studies, or meta-analyses of TH for near-hanging patients.We limited the search to human literature; we did not limit language. Information extracted included number of patients, length of cooling, length of rewarming, outcome, complications, associated cardiac arrest, TH, and the quality of each study. We reviewed the literature pertaining to pathophysiology of near hanging and ischemia–reperfusion injury. We also reviewed the literature pertaining to major published guidelines in this area.

Results

We identified seven studies involving TH for near-hanging victims. There are no randomized controlled trials on TH in near hanging. The few studies found are either case reports or retrospective reporting of case series (Table 1). In all studies, the patient population comprised solely of near-hanging victims, most of whom received TH, except one study (Baldursdottir et al., 2010) that included near-hanging victims in addition to patients with drowning, carbon-monoxide intoxication, and other gas intoxications. We only collected data on near-hanging patients. All patients were comatose on admission to the ICU; some patients sustained cardiac arrest. When TH was used, the target temperature of 32–33°C was used in all studies; length of cooling ranged from 24 to 36 hours, except for one patient who received TH for 43.5 hours (Borgquist and Friberg, 2009). The outcome in all studies was evaluated at ICU or hospital discharge. The primary outcome measure was neurological function, as determined by the five-levelled cerebral performance category (CPC) scale (Cummins et al., 1991). The outcome of patients was classified as good or poor, with a good outcome equivalent to a CPC of 1 or 2 (conscious, able to carry out independent activities), and a poor outcome equivalent to a CPC of 3–5 (conscious but dependent on others for daily support, unconscious, or dead).

Table 1.

Studies That Reported the Effects of Therapeutic Hypothermia on Outcome in Near-Hanging Patients

Reference	No. patients	Cardiac arrest	No cardiac arrest	TH	Length of cooling (hours)	Length of rewarming	Complications	Good outcome (n, %)
Legriel et al. (2005)	1	1	0	All	36	—	None	1, 100%
Lund-Olsen et al. (2008)	1	0	1	All	36	—	None	1, 100%
Borgquist and Friberg (2009)	13	3 (VF, asystole, unknown)	10	8 (3 CA+5 no CA)	26 (11–43.5)	—	Pneumonia (85%) Seizures (31%) Pneumothorax (7.7%)	All: 9, 69% TH: 6, 75%
Baldursdottir et al. (2010)	8	6	2	All	24	0.5°C/hour	None	5, 62.5% (3 bad outcomes had CA)
Jehle et al. (2010)	2	0	2	All	24	—	None	2, 100%
Sadaka et al. (2010)	1	0	1	All	24	12	None	1, 100%
Lee et al. (2012)	25	16 (15 non-VF arrest)	9	17 (13 CA+4 no CA)	24	0.25°C/hour	Pneumonia (23.5%)	All: 4, 20% TH: 5, 30% CA: 1, 6.2% No CA: 9, 100%

TH, therapeutic hypothermia; CA, cardiac arrest; VF, ventricular fibrillation.

Legriel et al. (2005) were the first to apply TH on one comatose near-hanging patient who suffered cardiac arrest, and the patient survived with good neurologic outcome. Lund-Olesen et al. (2008) applied TH on a comatose near-hanging patient without cardiac arrest, and again the patient survived with good neurologic outcome. Borgquist and Friberg (2009) retrospectively identified 13 comatose near-hanging patients who were treated in the ICU. Overall outcome was good in nine patients (69%). The majority of the patients received TH (8/13), and among them were three patients with cardiac arrest. Outcome was good in six of eight patients who received TH, and in one of the three patients who suffered cardiac arrest. Among the 10 patients without cardiac arrest, five patients received TH, and all five recovered well, whereas two of five patients not receiving TH died. Jehle et al. (2010) reported a case series of two patients who received TH for their comatose state after near-hanging injury without cardiac arrest; both patients recovered without neurological sequelae. We reported one patient, comatose after near hanging with no cardiac arrest, who survived to hospital discharge with full neurologic recovery (Sadaka et al., 2012). Finally, Lee et al. (2012) reviewed 25 unconscious near-hanging cases who were admitted to the ICU. Sixteen had experienced cardiac arrest at the scene (15/16 had non-VF arrest). Of the 16 patients who had cardiac arrest at the scene, 13 were treated with TH; the other three did not receive TH because their next of kin refused. All cardiac-arrest patients, with the exception of one, had poor outcomes at the time of discharge. Nine patients did not have cardiac arrest. Four of the nine patients who did not have cardiac arrest received TH, but the other five patients did not because of refusal by the patients' next of kin. All patients who did not have cardiac arrest showed good outcomes at the time of discharge.

Next, we combined patients from all the studies and looked at outcomes concerning cardiac arrest and TH (Fig. 1). A total of 51 comatose near-hanging patients were included. Out of the 26 patients who suffered cardiac arrest, 23 received TH, and three did not. Of the 23 patients who received TH, six patients (26%) had good neurologic recovery, whereas 17 (74%) had poor outcome. All three cardiac-arrest patients who did not receive TH had poor outcomes. Out of the 25 patients who did not suffer cardiac arrest, 15 received TH and 10 did not. All 15 patients who received TH versus eight patients (80%) who did not receive TH had good outcomes (Fig. 1).

FIG. 1.

Near-hanging victims in coma from all the studies combined. Good and poor outcomes are presented concerning cardiac arrest and therapeutic hypothermia.

Discussion

The presence of brain anoxia seems to be a powerful predictor of poor outcome in near-hanging patients (Salim et al., 2006). That also explains why patients who sustain cardiac arrest, irrespective of application of TH, do worse than those who do not sustain cardiac arrest, since the presence of cardiac arrest reflects a longer duration of ischemia and thus worse severity of brain injury. It also seems that the cardiac arrest resulting from asphyxia from near hanging is a non-VF arrest, mainly asystole and pulseless electrical activity, which carries a worse prognosis than VF arrest. Since most suicidal hanging attempts are not witnessed, the time to return of spontaneous circulation (ROSC) tends to be longer in patients experiencing cardiac arrest after near hanging than in patients with VF cardiac arrest. In addition, asphyxial cardiac arrest has been known to cause more severe and widespread injury than VF cardiac arrest of the same duration (Vaagenes et al., 1997).

Does the application of TH benefit near-hanging patients who sustain cardiac arrest? This patient population has not been studied in large randomized controlled studies, primarily because non-shockable rhythms (experienced by near-hanging victims) were excluded from most studies on TH for cardiac arrest. From the studies reviewed in this manuscript, 26% of near-hanging arrest patients who received TH had a good outcome compared to 0% of near-hanging arrest patients who did not receive TH (Fig. 1). However, the numbers are too small to draw any conclusions. Because of the limited evidence, TH for non-shockable rhythms was assigned a lower level of evidence recommendation. The most recent guidelines by the European Resuscitation Council and the American Heart Association in 2010 recommend that induced hypothermia (32–34°C for 12–24 hours) may be considered for comatose (i.e., lack of meaningful response to verbal commands) adult patients with ROSC after in-hospital cardiac arrest of any initial rhythm or after out-of-hospital cardiac arrest with an initial rhythm of pulseless electrical activity or asystole (Class IIb) (Peberdy et al., 2010). Near-hanging patients who suffer cardiac arrest (mainly out-of-hospital cardiac arrest with an initial rhythm of pulseless electrical activity or asystole) fall within this category, unless they sustain a VF arrest (rare), then TH becomes a Class I recommendation (Peberdy et al., 2010).

Does the application of TH benefit near-hanging patients who do not sustain cardiac arrest? It is reasonable to assume that victims of near hanging suffer from ischemia–reperfusion injury, irrespective of whether they sustained cardiac arrest. This is precisely the premise for why TH was attempted on this patient population in these studies to begin with. Some studies showed that near-hanging victims who present comatose to the hospital can have good neurologic outcomes after supportive therapy alone (Howell and Guly, 1996; Penney and Stewart, 2002). However, some patients are still left with poor neurologic outcome presumably from ischemia–reperfusion injury to the brain. From the studies reviewed in this manuscript, 100% of near-hanging patients without cardiac arrest who received TH had a good outcome compared to 80% of near-hanging patients without cardiac arrest who did not receive TH (Fig. 1). Again, the numbers are too small to draw any conclusions. A prospective study is warranted to test the potential benefit of TH on neurologic outcome and survival in this patient population. Although it would be difficult to conduct such a study, we feel that the compelling case studies, anecdotal evidence, and extrapolated data support the following recommendation: “Induced hypothermia (32°C to 34°C for 12 to 24 hours) may be considered for comatose (i.e., lack of meaningful response to verbal commands) adult near-hanging patients.”

All reviewed studies have obvious limitations. They are all retrospective and therefore some data may be missing. The number of patients is small, the groups are not matched, and some are case reports. Furthermore, neurological outcome was categorized by chart review and not by direct patient assessment. Finally, the CPC scale offers broad categories, which makes it a relatively inaccurate assessment tool for neurological impairment. However, this is the scale used to assess outcomes in cardiac-arrest studies so far.

Conclusion

Even though some studies showed that near-hanging victims who present comatose to the hospital can have good neurologic outcomes after supportive therapy alone, some patients are still left with poor neurologic outcome, presumably from ischemia–reperfusion injury to the brain. Hence, a prospective study is warranted to test the potential benefit of TH on neurologic outcome and survival in this patient population. Although it would be difficult to conduct such a study, we feel it is reasonable to offer TH to near-hanging victims with cardiac arrest. We also suggest that comatose near-hanging patients without cardiac arrest may be considered for TH.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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