Carrie Harvey and Ivan Nathaniel Co
Abbreviations
°C Degrees Celsius
ACLS Advanced Cardiac Life Support AHA American Heart Association CAVR Continuous arteriovenous
rewarming
CPB Cardiopulmonary bypass CPR Cardiopulmonary resuscitation CVVHD Continuous venovenous
hemodiafiltration
CVVR Continuous venovenous rewarming
CXR Chest x-ray
ECG Electrocardiogram
EMS Emergency Medicine Services IV Intravenous
PRBC Packed red blood cells
VA-ECMO Venoarterial extracorporeal membrane oxygenation VF Ventricular fibrillation VT Ventricular tachycardia VV-ECMO Venovenous extracorporeal
membrane oxygenation
Case Presentation
A 64 year old male with a history of hypertension and prostate cancer was found unresponsive by his wife around 0800 in their driveway in the mid- dle of February in Toledo, OH. His wife had gone to bed before him the night prior and did not real- ize he was missing until approximately 9 h later.
He was found on his side in a snow bank near the mailbox. Ambient temperature was approxi- mately −2° Fahrenheit. He was unresponsive to painful stimuli. Emergency Medical Services (EMS) was called and the patient was transported to the nearest Level I Trauma center with full car- diac surgery capabilities. Transport vital signs included undetectable temperature by temporal probe, heart rate of 45 beats per minute, blood pressure of 60/palpation, and agonal respirations.
En route, he received 2 L of warmed crystalloid and was intubated for airway protection. Vital signs on arrival to the Emergency Department were remarkable for heart rate of 20 beats per minute and blood pressure of 50/30. His axillary temperature was unable to be obtained. Foley catheter was placed and bladder temperature was 24 °C. Primary survey revealed clear breath sounds bilaterally, pupils 5 mm and fixed bilater- ally, and Glascow Coma Scale (GCS) score of 3.
His clothing was removed with no external signs of trauma. Cervical spine immobilization was maintained with a hard cervical collar applied by EMS prior to arrival. Electrocardiogram (ECG) was obtained with sample rhythm strip shown in
C. Harvey (*)
Department of Anesthesiology, University of Michigan Health System, Ann Arbor, MI, USA e-mail: [email protected]
I.N. Co
Division of Pulmonary and Critical Care Medicine, University of Michigan,
Ann Arbor, MI, USA
9
Fig. 9.1. Initial arterial blood gas on FiO2 1.0 was as follows: pH 6.73, paCO2 50 mmHg, paO2
259 mmHg, bicarbonate 4.8 mmol/L, base deficit
−29.7, SaO2 98 %, potassium 5.2 mmol/L, and hemoglobin 13.6 mmol/L. Toxicology screen was negative. Active rewarming with warm humidi- fied air, warm intravenous fluids, and warm fluid lavage of the stomach and bladder was initiated.
After 30 min, pulse was unobtainable with ven- tricular fibrillation noted on telemetry.
Cardiopulmonary resuscitation (CPR) was initi- ated and he was defibrillated once at 200 J. Ventricular fibrillation persisted and repeat core temperature was 25 °C.
Question What is the next best step in rewarm- ing this patient?
Answer Initiate rewarming via extracorporeal cardiopulmonary resuscitation (ECPR)
When pulse and signs of life are absent in hypothermia, treatment with extracorporeal rewarming with extracorporeal membrane oxy- genation (ECMO) or cardiopulmonary bypass (CPB) is recommended. ECMO can be initiated in two modes: veno-venous (VV) or veno-arterial (VA) depending on the presence of innate and pre- served cardiac function. This hospital has cardiac
surgery available and consultation with the sur- geon is necessary to determine which modality is best for the patient. Due to ongoing CPR, the decision was made to initiate VA ECMO with per- cutaneous venous and arterial cannulation at the bedside. The heater on the ECMO circuit was set to 37 °C and rewarming was started as soon as cannulation was complete. CPR continued until the patient was rewarmed to 30 °C, at which point defibrillation was again attempted with successful conversion to normal sinus rhythm. After 4 h of ECMO, his temperature and blood pressure had normalized. Repeat arterial blood gas on FiO2 0.5 was: pH 7.38, paCO2 39 mmHg, paO2 92 mmHg, bicarbonate 22.6 mmol/L, base deficit −2.2, SaO2
99 %, potassium 3.7 mmol/L, and hemoglobin 10.5 mmol/L. He received broad- spectrum antibi- otics for high likelihood of aspiration and contin- ued warm IV fluids due to presumed cold diuresis.
After 24 h, the patient was awake and following commands with no evidence of acute respiratory distress syndrome. ECMO support was stopped and the patient was extubated the following day without incident. Neurologic exam was normal.
He developed AKI requiring 3 days of dialysis, but had complete renal recovery. He was dis- charged home after 1 week with no functional or neurologic impairment.
Fig. 9.1 Classic electrocardiogram findings in hypothermia. This EKG demonstrates three common findings in hypo- thermia, including bradycardia, shivering artifact, and J-waves (Image courtesy of lifeinthefastlane.com)
Principles of Management Diagnosis
Hypothermia is defined as a core body tempera- ture of less than 35 °C (95 °F) and is classified by severity; mild, moderate, or severe (Table 9.1) [1]. Standard thermometers do not read below 34 °C, therefore, accurate measurement of core temperature should be obtained by esophageal, bladder, or rectal probes [2]. If core temperature cannot be readily measured, the Swiss staging system (Table 9.2) can be used to guide manage- ment based on clinical symptoms [3]. Additional risk factors for development of accidental hypo- thermia include extremes of age, ethanol abuse, and malnutrition [2].
With cold exposure, the body attempts to increase heat production by increasing circulat- ing epinephrine, which leads to tachycardia, increased minute ventilation, peripheral vasocon- striction, and shivering [4]. If exposure persists, these compensatory mechanisms are over- whelmed, resulting in decreased metabolic demand, cessation of shivering, and ultimately death [3]. The effects of hypothermia by organ system are summarized in Table 9.3 and repre- sent typical clinical findings.
Finally, any underlying medical conditions that may have contributed to development of
hypothermia should be obtained by a focused his- tory and physical exam. These include trauma, infection, toxic ingestion, endocrinopathy (e.g.
myxedema coma), metabolic derangements, and stroke [1].
Patient Monitoring
Due to the dramatic hemodynamic changes that can occur with hypothermia and rewarming, all patients should be closely monitored with telemetry, continuous pulse oximetry, frequent blood pressure checks, and core temperature probe [3]. Pulse oximetry is often difficult to measure due to peripheral vasoconstriction and arterial blood gas may be the only way to assess oxygen content. There is also limited data to suggest that forehead pulse oximetry may be more accurate than fingertip devices in hypo- thermia [5]. The authors recommend pre-emp- tive placement of defibrillator pads if there is any concern for development of ventricular dysrhythmias. The prognostic value of end- tidal carbon dioxide monitoring in cardiac arrest secondary to accidental hypothermia has not been studied.
Adjunctive Testing
Once the diagnosis of hypothermia is confirmed by core temperature measurement, additional testing should include basic laboratory studies, toxicology screen, ECG, and chest radiograph (CXR). Typical laboratory findings are listed in Table 9.4. Slowed cardiac conduction manifests as a variety of ECG changes, the most common of which is the Osborne wave (Fig. 9.2), seen in approximately 80 % of hypothermic patients [7].
Baseline CXR is recommended due to the inher- ent risk of aspiration pneumonia in this patient population. CT head imaging in all hypothermic patients is not clearly indicated but should be considered if altered mental status is present despite temperature >32 °C or signs of head trauma are present [1]. Further workup should be pursued on an individual basis if associated
Table 9.1 Classification of hypothermia
Mild 35–32 °C
Moderate <32 to 28 °C
Severe <28 to 24 °C
Table 9.2 Swiss staging system of hypothermia Stage Clinical symptoms
I Conscious, shivering
II Altered mental status, no shivering III Unconscious, no shivering IV No vital signsa
Data from Brown et al. [3]
The estimated core temperature in stage I, II, and III cor- respond to mild, moderate, and severe hypothermia, respectively
aLoss of vital signs general occurs when the core tempera- ture is below 24 °C
trauma, infection, or other medical condition is suspected.
Rewarming
There are four general approaches to rewarming:
passive, active external, active internal, and extra- corporeal [8]. The best method depends on the severity of hypothermia and resources available to the provider, although there are no random- ized, controlled trials regarding treatment approach. The average rates of rewarming for each method are listed in Table 9.5.
Passive rewarming is applicable to all hypo- thermic patients and should begin in the pre- hospital setting, with removal of wet clothing, application of blankets or foil insulator, and pro- tection from the environment [9]. This method alone is only effective if shivering is present, oth- erwise, active rewarming is necessary.
Active external rewarming assumes circula- tion is intact and can return warmed blood to the core. Examples include warm blankets, radiant heat lamps, forced air device (e.g. Bair HuggerTM), and warm water immersion [10].
Active internal rewarming includes warm humidified air (42 °C), warm intravenous (IV) fluids (42 °C), body cavity lavage (gastric, tho- racic, peritoneal, bladder), intravascular devices, and peritoneal dialysis [1, 11]. If a commercial fluid warmer is not available, non-dextrose con- taining fluids can be warmed in a conventional
microwave and then shaken to ensure uniform heating prior to infusion [12].
Extracorporeal rewarming is the most effec- tive method, with up to 6 °C/h rate of rewarming, but also the most invasive and resource intensive [13, 14]. Hemodialysis is generally the most readily available, but requires an adequate blood pressure to tolerate the procedure. Continuous arteriovenous rewarming (CAVR) or continuous venovenous rewarming (CVVR) can be achieved via percutaneous access and a countercurrent
Table 9.3 Clinical findings in hypothermia
Organ system Mild Moderate Severe
Neurologic Apathy
Confusion Ataxia
Dilated pupils Paradoxical undressing Stupor
Areflexia Coma
Cardiovascular Tachycardia Bradycardia
Atrial fibrillation Hypotension
Ventricular dysrhythmias Asystole
Pulmonary Tachypnea Bradypnea Pulmonary edema
Renal High urine output High urine output Oliguria
Metabolic Hyperglycemia
No shivering Respiratory alkalosis
Variable blood glucose Shivering
Mixed metabolic and respiratory acidosis
Hypoglycemia No shivering Mixed metabolic and respiratory acidosis Data from Mulcahy and Watts [1]
Table 9.4 Common laboratory derangements in hypothermia
Test
Typical
result Comments Hematocrit High Due to
hemoconcentration from cold dieresis
Potassium High Potassium > 12 mmol/L considered universally fatal [3, 6]
Creatinine High Creatine
kinase
High Should be checked routinely as time down often unknown PT/PTT High Due to coagulation
cascade enzyme denaturation at colder temperature; reported values may be normal as blood heated prior to testing
Arterial blood gas
Variable Recommend using uncorrected values [1]
Lactate High
heat exchanger (e.g. Belmont® Rapid Infuser) [15, 16]. Both methods utilize the patient’s blood pressure to drive the blood through the device.
CVVR by continuous venovenous hemodiafiltra- tion (CVVHD) has also been shown to be effec- tive in a case report [17]. Veno-arterial ECMO and CPB require the most resources and exper- tise, but bypasses the native circulation and can therefore be used in patients in cardiac arrest.
For patients with stable hemodynamic parameters, active rewarming with a forced air device, warm humidified air, and warm IV fluids is generally sufficient to achieve normothermia [18]. If these initial measures are not sufficient, a patient can undergo more invasive rewarming.
Thoracic lavage and ECMO carry considerable risk and should be reserved for those patients with cardiac instability [11]. Expert opinion rec- ommends ECMO if required resources are available [3, 11].
Hypothermia Without a Pulse
The 2010 American Heart Association (AHA) guidelines provide recommendations on advanced cardiac life support (ACLS) modifica- tions in hypothermia, although these are based on expert opinion and case reports only (level of evi- dence C):
(a) If a patient does not have a pulse, ACLS should be immediately initiated, unless one of the fol- lowing is present: valid Do Not Resuscitate order, patient is frozen solid, there is ice in the airway, core temperature is <10 °C, the patient was submerged for more than 1 h, or there is obvious lethal injury [1, 3, 19].
(b) If ventricular fibrillation (VF) or ventricu- lar tachycardia (VT) is present, defibrilla- tion should be attempted [20]. The number of attempts that should be made if VF or VT persists has not been established. The AHA guidelines state that it may be reason- able to perform further defibrillation (Class IIb recommendation), while most treatment algorithms recommend only one shock until the patient is rewarmed to 30 °C [1, 3].
(c) There is a theoretical concern for toxic accumu- lation of ACLS drugs due to reduction in drug metabolism in severe hypothermia. The AHA guidelines state that the safety of administration or withholding of medication is unclear, but that it is reasonable to consider administration of a vasopressor according to standard ACLS guide- lines (Class IIb recommendation). Similarly,
Fig. 9.2 Osborne wave.
Osborne wave, or J wave, is frequently seen in hypothermia, although it is not pathognomonic for the condition. It is character- ized by a positive deflection at the J point (negative in aVR and V1) and is usually seen best in the precordial leads. The height of the J wave generally corresponds to the degree of hypother- mia [7] (Image courtesy of lifeinthefastlane.com)
Table 9.5 Rewarming techniques
Technique Rate (°C/h)
Removal of wet clothing, insulation 0.5 Warm environment, warm oral fluids, active movement
2 Forced-air heating device, warm IV fluids 0.1–3.4
Peritoneal dialysis 1–3
Hemodialysis 2–4
Thoracic lavage 3
Venovenous ECMO 4
Venoarterial ECMO 6
Cardiopulmonary bypass 9
Data from Brown et al. [3]
expert opinion recommends up to three doses of epinephrine, with re-evaluation once the patient is rewarmed to 30 °C [3, 18].
In patients with return of spontaneous circula- tion after cardiac arrest, multi-organ failure should be anticipated and treated similar to any other critically ill patient.
Other Supportive Care
The majority of patients will present with hypovo- lemia secondary to cold diuresis and will conse- quently require aggressive fluid resuscitation. In one study of 38 severely hypothermic patients who received warmed IV fluids, the average vol- ume load was 4.8 L [20]. Hyperglycemia (mild hypothermia) and hypoglycemia (severe hypo- thermia) are also common, thus, serum glucose level should be obtained and treated accordingly.
Alcohol intoxication should prompt consideration of thiamine and alert the provider to the potential for alcohol withdrawal. It is recommended that broad-spectrum antibiotics be given to those patients at risk for associated infection, such as neonates, the elderly, and the homeless, as those with infection often respond poorly to rewarming [21]. There is no evidence for empiric steroids, unless there is high clinical suspicion for adrenal insufficiency as the cause of hypothermia [1].
Disposition
Those patients who presented with mild hypo- thermia that responded to rewarming methods, have a clear history of cold exposure, and have no evidence of an underlying disease or injury can be safely discharged home. All other patients require hospital admission, usually to the inten- sive care unit (ICU), for continued monitoring and supportive care.
In patients with cardiac arrest, the survival rate without neurologic impairment is higher in patients treated with ECMO (47–63 %) as compared to those without (<37 %) [3, 22, 23]. Therefore, patients with cardiac instability or arrest should be taken to the nearest facility capable of these inter-
ventions whenever possible. There are no guide- lines regarding inter-hospital transfer and this decision should be made on a case-by-case basis with the consulting cardiac surgeon.
As mentioned above, there are certain circum- stances in which CPR should not be initiated.
Some experts also provide recommendations on when to stop an ongoing resuscitation. All experts agree that a patient should receive aggressive resuscitation including CPR until core tempera- ture is at least 30 °C. A recent review article sug- gests that if asystole secondary to hypothermia persists despite rewarming to 32 °C, termination of CPR should be considered as the cardiac arrest is likely irreversible [3]. Similarly, markedly ele- vated potassium is considered a marker of hypoxia before hypothermia and therefore negatively associated with outcome. Most experts agree that resuscitation is futile if the potassium level is
>12 mmol/L [3, 6]. The highest potassium level in patients that survived was 7.9 mmol/L in an adult [23] and 11.8 mmol/L in a child [24].
Pediatric Patients
In general, the management of pediatric acciden- tal hypothermia is the same as adults. Pediatric Advanced Life Support (PALS) should be used in place of the ACLS algorithm. Pathophysiology and principles of rewarming are similar, with suc- cessful resuscitation via ECMO and CPB reported in the pediatric population. Hypothermia second- ary to submersion is more common in pediatric patients and carries a worse prognosis due to asso- ciated asphyxia. The longest duration of submer- sion with full neurologic recovery was 66 min and used ECMO for rewarming [25]. Guidelines for cessation of resuscitation are similar to adults.
Evidence Contour Withholding CPR
As stated above, the 2010 AHA guidelines rec- ommend ACLS if a pulse cannot be palpated.
However, it can be difficult to palpate a pulse in a
cold, stiff patient and many experts now advocate that CPR should be held if other signs of life are present, which include spontaneous respirations, spontaneous movement, or adequate cardiac activity is visualized on bedside echocardiogra- phy [1, 3]. Given the profound decrease in meta- bolic demand, it is hypothesized that any organized rhythm (i.e. bradycardia or adequate echocardiographic evidence of cardiac activity) provides enough perfusion to the body in hypo- thermia. Additionally, there is a long-standing belief that sudden movement of a hypothermic patient may irritate the myocardium and induce a dysrhythmia, such as in CPR [26]. This hypoth- esis has never been directly studied in humans.
Thus, in a hypothermic patient with a pulse, spontaneous movement and/or respiration, or with bedside echo evidence of adequate cardiac activity, ACLS should be held. Otherwise, con- tinuation of ACLS should be initiated per the AHA guidelines.
Degree of Rewarming in Cardiac Arrest
Given the neuroprotective effect of induced hypothermia following cardiac arrest, it is recom- mended that a patient with accidental hypother- mia and cardiac arrest undergo therapeutic hypothermia for 24 h.
Timing of Extracorporeal Support
It remains unclear if aggressive extracorporeal rewarming with VA or VV ECMO should be ini- tiated in patients without associated cardiac arrest. Some authors do recommend ECMO in patients with hemodynamic instability who do not respond to initial medical management [3].
Conversely, one prospective study of 38 patients with severe hypothermia without cardiac arrest found that 92 % of the patients could be success- fully rewarmed to normothermia via forced air device, warmed inhaled oxygen, and warmed IV fluids within 10 h, including 14 of 17 patients with unstable hemodynamic parameters [20].
Selection of Extracorporeal Support There are no randomized controlled trials com- paring the various rewarming modalities.
Expert opinion recommends that a hypother- mic patient who has hemodynamic instability following accidental hypothermia should undergo extracorporeal support. VA ECMO is the mode of ECMO preferred as it provides cardiac support in addition to rewarming [27].
Selection of modality for rewarming will depend on resources available at the physi- cian’s institution.
Transcutaneous Pacing
Classic teaching in hypothermia has been to avoid any manipulation of the heart rate due to concern of inducing a ventricular dysrhythmia. However, a case report of two patients reported successful rewarming using CAVR with concomitant trans- cutaneous pacing [28]. In both cases, pacing was required to maintain blood pressure so that CAVR could be used. There were no reported dysrhyth- mias and both patients had normal neurologic out- comes. Still, it is hypothesized that bradycardia and hypotension in hypothermia may not be harmful due to the reduced metabolic require- ments. A trial of transcutaneous pacing is reason- able but should not delay the initiation of rewarming.
Endovascular Rewarming
Successful rewarming of a patient using an endo- vascular device has been reported [29, 30]. This device is the same as those used for therapeutic hypothermia following cardiac arrest, which requires only percutaneous central venous access.
This method had a rewarming rate of 3 °C/h, which is similar to thoracic lavage and may there- fore be an efficient, less invasive alternative in facilities in which extracorporeal rewarming is not available. Similar to other active internal methods, the endovascular approach requires that the patient have a pulse.