Cold critters: Understanding hypothermia

Hypothermia, or subnormal body temperature, may be classified as primary or secondary.1 Primary hypothermia typically results from environmental exposure despite normal heat production by the body.2 Secondary hypothermia results from alterations in heat production because of illness, injury, or drugs.3,4 Understandably, secondary hypothermia may frequently influence morbidity and mortality in critically ill animals.

Photo by Greg Kindred

HEAT LOSS

There are four basic mechanisms of heat loss5:

• Convection transfers heat from the body surface to air moving past the animal.

• Conduction transfers heat from the body surface to colder objects in contact with the skin.

• Radiation is the exchange of heat between the body and objects in the environment that are not in contact with the skin, independent of the temperature of the surrounding air.

• Evaporation occurs when moisture in contact with skin or the respiratory tract dissipates into the air.

Heat production due to the body's various metabolic processes is directly proportionate to body mass, and, thus, cutaneous heat loss is a function of body surface area.6 Small companion animals have higher surface-area-to-body-mass ratios that make them uniquely susceptible to heat loss. Additionally, cachectic, debilitated, immobile, and critically ill patients have impaired thermoregulatory capabilities and may not be able to retain or seek heat.

THERMOREGULATION

Receptors for cold and warm are distributed throughout the body. Cold signals traverse A-delta fibers, and signals from warmth receptors are relayed through C fibers.7 Processing thermoregulatory information occurs through three pathways7: afferent thermal sensing from the periphery, central regulation in the hypothalamus, and efferent responses.

Given these three pathways, peripheral body temperatures are constantly fluctuating while the posterior hypothalamic thermoregulatory center maintains a relatively constant core temperature.8 Cellular metabolism results in heat production by the body, and heat is lost from the body when core heat is transferred through variably conductive tissues to the skin and is subsequently lost to the environment.6 Specifically, heat is transferred from the body's core to the skin through a multitude of blood vessels, including venous plexuses and capillaries, with arteriovenous connections that are under the control of the autonomic nervous system.9,10 The rate of blood flow through these arteriovenous anastomoses varies depending on the degree of vasoconstriction or vasodilation desired.9,10 Increased blood flow leads to increased heat loss, whereas decreased blood flow results in core heat conservation.5

HYPOTHERMIC SPIRAL

As core body temperature dips below 94 F (34.4 C), thermoregulation is impaired, and animals characteristically cease to shiver or seek heat.11 Peripheral vasodilation rather than vasoconstriction predominates, leading to continued core heat loss.12 Additionally, heat production decreases because of the decreased metabolic rate.4,6 Concurrently, severe hypothermia depresses the central nervous system, ultimately resulting in a hypothalamus that is less responsive to hypothermia.6 Indeed, when the body core temperature drops below 88 F (31.1 C), thermoregulation ceases.5

POTENTIAL COMPLICATIONS

Cardiac effects

Common electrocardiographic changes seen with hypothermia include sinus bradycardia, an increased Q-T interval, and the J, or Osborn, wave (Figure 1).13,14 In people, sinus bradycardia and decreased T wave voltage are seen at 95 F (35 C), and with progressed hypothermia there is prolongation of the P-R and Q-T intervals and QRS complex. In dogs and cats, the J wave is typically seen at temperatures from 86 to 93.2 F (30 to 34 C), and there is usually atrial fibrillation or ventricular irritability that terminates as ventricular fibrillation at temperatures below this rate.13,15-17

1. The J wave seen on this electrocardiogram is related to body temperature. It results from a voltage gradient between the epicardium and endocardium that, in turn, produces a prominent epicardial action potential notch.

The prominence of the J wave is related to body temperature, and its genesis is related to dysfunction of the intramyocardial M cells.18 This dysfunction results from a voltage gradient between the epicardium and endocardium that, in turn, produces a prominent epicardial action potential notch.18 This abnormal deflection is more or less present and prominent in each electrocardiographic plane, and the wave occurs as a convex elevation at the junction of the QRS complex and the S-T segment.19

The responsiveness of alpha-1 adrenergic receptors decreases in dogs and cats with decreased core temperatures. Initially, alpha-1 receptor catecholamine binding increases, but with prolonged and progressive hypothermia, there is decreased receptor affinity. Reduced receptor binding results in a diminished contractile response and, ultimately, vasodilation of the cutaneous veins.20 Previous studies have demonstrated hypersensitivity in beta-1 receptors during hypothermia; additionally, alpha-1 adrenoceptor-mediated vasoconstriction was attenuated while alpha-2 adrenoceptor response was unaffected.21,22 Both alpha and beta adrenoceptors are desensitized in people with hypothermia associated with cardiopulmonary bypass.23 Hypothermia around 95 F (35 C) is associated with markedly decreased left ventricular contractility and leads to reduced cardiac output and impaired diastolic relaxation in neonatal pigs.24,25 Cardiac function in dogs with experimentally induced hypothermia is characterized by an initial period of increased ventricular contractility followed by decreased contractility at temperatures less than 68 F (20 C).26 Ventricular fibrillation was documented in 50% of the dogs with temperatures below 74 F (23.3 C).26

Pulmonary effects

Severe hypothermia causes a reduction in both respiratory rate and tidal volume because of decreased cellular metabolism and lowered carbon dioxide production, thus diminishing the stimulation of ventilation.27-29 Patients with subnormal body temperatures also have a blunted response to carbon dioxide, but the degree of oxygen use concurrently decreases, leaving the respiratory quotient unaffected.30 The shifting of the oxygen-hemoglobin dissociation curve to the left, blood sludging, and a decline in alveolar ventilation may lead to hypoxia, pulmonary edema, acute respiratory distress syndrome, or pneumonia.31-33 Patients that experience near-drowning initially hyperventilate secondary to the mammalian dive reflex, potentially resulting in an alkalosis that may exacerbate a left shift of the oxygen-hemoglobin dissociation curve. Severely hypothermic patients may hypoventilate, possibly contributing to the development of acidosis.

Clinical pathology effects

Hypoglycemia and hypothermia frequently occur concurrently, and low blood sugar may exacerbate a decrease in metabolic activity that may perpetuate hypothermia.34,35 Hypokalemia is commonly documented in patients with hypothermia and is a result of intracellular shifting (rather than true loss) that is thought to be due to a temporary depression in the function of the potassium pump mechanism in the cell membrane.36,37 Potassium derangements secondary to hypothermia must be monitored for and carefully corrected to avoid the development of dysrhythmias or perfusion abnormalities, particularly during rewarming.36-39

Hypothermia-induced coagulation abnormalities include reversible platelet sequestration and decreased platelet thromboxane production, granule secretion, and von Willebrand factor expression leading to decreased platelet aggregation, as well as enhanced fibrinolytic activity and slowing of enzymatic activity required for clotting.40 One study showed surface cooling to 89.6 F (32 C) induced reversible platelet dysfunction, and another study showed bleeding time in pigs doubled at 86 F (30 C).41,42 Coagulation abnormalities may be easily missed in the clinical setting because most coagulation tests are conducted at 98.6 F (37 C), potentially preventing identification of a coagulopathy present at hypothermic temperatures. Hypothermia-induced coagulation disorders rapidly reverse once normothermia is reestablished.41

Hypothermia induces diuresis and a reduction in glomerular filtration rate, which is secondary to both a reduced release of vasopressin and a reduction in renal medullary hypertonicity.43 With progressive hypothermia, hypovolemia and subsequent mild increases in hematocrit and blood viscosity develop.44 Hemoconcentration and low microcirculatory flow increase blood viscosity by 4% to 6% for each one degree Celsius that body temperature declines.44 Suppression of antidiuretic hormone and core-directed shunting of peripheral blood induce diuresis in hypothermic states that may contribute to hypovolemia.45,46

Neurologic effects

Cerebral blood flow and cerebral autoregulation are adversely affected by declining body temperature, most frequently resulting in mentation changes.31 Cerebral metabolic rate and cerebral blood flow decrease about 5% for each one degree Celsius drop in body temperature.47 Severe hypothermia is associated with abnormal neurologic signs ranging from depression to coma. Hypothermia also results in decreased metabolism of anesthetic agents, potentially prolonging recovery and affecting mentation in postoperative patients.31 A previous study showed mild hypothermia conveyed a cerebral protective benefit against ischemia during resuscitation without inducing cardiovascular consequences; interestingly, moderate hypothermia resulted in cardiovascular decompensation despite conferring neurologic benefits.48

Immune system effects

Hypothermia causes vasoconstriction and a left shift of the oxygen-hemoglobin curve that leads to impaired oxygen delivery to tissues and may be associated with a diminished resistance to infection.49,50 Tissue hypoxia is associated with impaired oxidative killing by neutrophils, and decreases in body temperature cause a reduction in phagocytosis, impaired chemotaxis, and pancytopenia, as well as a depression of the production of cytokines and antibodies.51

People with postoperative hypothermia have poor wound healing and increased incidence of infection.52 Wound healing is further impaired by tissue hypoxia because hydroxylases required for granulation tissue depend on adequate oxygen tension.51 A previous study clearly showed wound cultures were significantly more often positive in patients with mild perioperative hypothermia compared with normothermic patients.52 However, a retrospective veterinary study showed no difference in infection rates in patients experiencing perioperative hypothermia.53

Anesthetic and surgical effects

General anesthesia and surgery readily result in primary and secondary hypothermia. Intubated patients inspire cold, dry air delivered directly to the lungs. Routine aseptic preparation of surgical sites promotes evaporative heat loss, and cold table surfaces and open body cavities will exacerbate heat loss through conduction and radiation, respectively. Anesthetic agents affect the hypothalamic thermoregulatory center in such a way that thermogenic responses are not triggered until low temperatures are reached.6 Centrally mediated thermoregulatory vasoconstriction is directly inhibited to cause peripheral vasodilation. Anesthesia decreases the metabolic rate by 15% to 40% and inhibits muscular activity to cause decreased heat production.4,6,54-56

Coagulopathy and platelet dysfunction logically represent serious complications in surgical or posttraumatic patients at risk for hemorrhage. Hypothermia delays anesthetic recovery and may lead to surgical complications such as dysrhythmias, hypotension, respiratory depression, bradycardia, coagulopathy, altered blood viscosity, and anesthetic drug overdose.57 Minimizing the duration of anesthetic and surgical procedures may reduce the incidence of secondary hypothermia.

Consequences following trauma

Hypothermia after trauma is common in people.58 Although there is a correlation between hypothermia and mortality, there is no threshold below which mortality is assured.58,59 A markedly hypothermic patient may initially appear deceased because of poor cardiac contractility, bradycardia, increased blood viscosity, and cold or stiff limbs. For this reason, you must thoroughly evaluate a patient with severe hypothermia, potentially using advanced diagnostic tests, such as electrocardiography, to ensure rapid identification and to afford rapid intervention.

Hypothermia in trauma patients is often proportional to the degree of shock and severity of tissue damage.24,60 Previous laboratory studies suggest that patients with hemorrhagic shock have increased survival with concurrent mild hypothermia compared with those whose resuscitation protocols included rewarming interventions, thus underscoring the potential benefit of hypothermia during low perfusion states.39,61

In Part 2 of this series, Cold critters: Assessing, preventing, and treating hypothermia, I describe three common rewarming methods, and I discuss when to apply these different methods and what rewarming complications you need to watch out for.

Christopher G. Byers, DVM, DACVECC, DACVIM (small animal internal medicine)

MidWest Veterinary Specialty Hospital

9706 Mockingbird Drive

Omaha, NE 68127

REFERENCES

1. Matsuzaki Y, Matsukawa T, Ohki K, et al. Warming by resistive heating maintains perioperative normothermia as well as forced air heating. Br J Anaesth 2003;90:689-691.

2. Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med 2009;37(7 Suppl):S186-202.

3. Smith TM, Berk AS, Upadhyay H. Severe hypothermia in a patient with spinal cord injury without radiological abnormality. J Emerg Trauma Shock 2011;4:421-424.

4. Sessler D. Temperature monitoring. In: Miller R, ed. Anesthesia. 4th ed. Philadelphia, Pa: Churchill Livingstone, 1994;1363-1382.

5. Guyton A. Body temperature, temperature regulation, and fever. In: Textbook of medical physiology. Philadelphia, Pa: WB Saunders Co, 1991;797-808.

6. Sessler DI. Perioperative heat balance. Anesthesiology 2000;92:578-596.

7. Kurz A. Physiology of thermoregulation. Best Pract Res Clin Anaesthesiol 2008;22:627-644.

8. Hammel HT. Regulation of internal body temperature. Annu Rev Physiol 1968;30:641-710.

9. Spence RJ, Rhodes BA, Wagner HN Jr. Regulation of arteriovenous anastomotic and capillary blood flow in the dog leg. Am J Physiol 1972;222:326-332.

10. Hales JR, Fawcett AA, Bennett JW, et al. Thermal control of blood flow through capillaries and arteriovenous anastomoses in skin of sheep. Pflugers Arch 1978;378:55-63.

11. Oncken A, Kirby R, Rudloff E. Hypothermia in critically ill dogs and cats. Compend Contin Educ Pract Vet 2001;23:506-521.

12. Roberts MF, Chilgren JD, Zygmunt AC. Effect of temperature on alpha-adrenoceptor affinity and contractility of rabbit ear blood vessels. Blood Vessels 1989;26:185-196.

13. Mareedu RK, Grandhe NP, Gangineni S, et al. Classic EKG changes of hypothermia. Clin Med Res 2008;6:107-108.

14. Slovis C, Jenkins R. ABC of clinical electrocardiography: conditions not primarily affecting the heart. BMJ 2002;324:1320-1323.

15. Olgers TJ, Ubels FL. The ECG in hypothermia: Osborn waves. Neth J Med 2006;64:350, 353.

16. Van Mieghem C, Sabbe M, Knockaert D. The clinical value of the ECG in noncardiac conditions. Chest 2004;125:1561-1576.

17. Gussak I, Bjerregaard P, Egan TM, et al. ECG phenomenon called the J wave: history, pathophysiology and clinical significance. J Electrocardiol 1995:28:49-58.

18. Wong FW. J wave and hypothermia. Dynamics 2005;16:17-18.

19. Pasquier M, Pasquier J, Vallotton L. J wave in hypothermia. J Trauma 2011;71:E99.

20. Flavahan NA, Lindblad LE, Verbeuren TJ, et al. Cooling and alpha 1- and alpha 2-adrenergic responses in cutaneous veins: role of receptor reserve. Am J Physiol 1985;249:H950-955.

21. Williams RG, Broadley KJ. Responses mediated via beta 1, but not beta 2-adrenoceptors, exhibit hypothermia-induced supersensitivity. Life Sci 1982;31:2977-2983.

22. Davis TR, Wood MB, Vanhoutte PM. The effect of hypothermic ischemia on the alpha-adrenergic mechanisms of the canine tibia vascular bed. J Orthop Res 1992;10:149-155.

23. Sellke FW, Tofukuji M, Stamler A, et al. Beta-adrenergic regulation of the cerebral microcirculation after hypothermic cardiopulmonary bypass. Circulation 1997;96(9Suppl):II-304-310.

24. Gregory JS, Flancbaum L, Townsend MC, et al. Incidence and timing of hypothermia in trauma patients undergoing operations. J Trauma 1991;31:795-798; discussion 798-800.

25. Dudgeon DL, Randall PA, Hill RB, et al. Mild hypothermia: its effect on cardiac output and regional perfusion in the neonatal piglet. J Pediatr Surg 1980;15:805-810.

26. Goldberg LI. Effects of hypothermia on contractility of the intact dog heart. Am J Physiol 1958;194:92-98.

27. Russel G. Induced hypothermia. In: Nunn J, Ulting J, Brown B, eds. General anesthesia. 5th ed. London, U.K.: Buttersworth, 1989;579-587.

28. Wetterberg T, Sjoberg T, Steen S. Effects of hypothermia in hypercapnia and hypercapnic hypoxemia. Acta Anaesthesiol Scand 1993;37:296-302.

29. Gaudy JH, Sicard JF, Gateau O, et al. [Respiratory effects of moderate hypothermia (36 degrees C-28 degrees C) in dogs under halothane anesthesia]. Can J Anaesth 1992;39:1094-1098.

30. Frank S. Consequences of hypothermia. Curr Anaesth Crit Care 2001;12:79-86.

31. Stoneham MD, Squires SJ. Prolonged resuscitation in acute deep hypothermia. Anaesthesia 1992;47:784-788.

32. Bloch M. Cerebral effects of rewarming following prolonged hypothermia: significance for the management of severe cranio-cerebral injury and acute pyrexia. Brain 1967;90:769-784.

33. Morales CF, Strollo PJ. Noncardiogenic pulmonary edema associated with accidental hypothermia. Chest 1993;103:971-973.

34. Carter WP Jr. Hypothermia—a sign of hypoglycemia. JACEP 1976;5:594-595.

35. Carter WP Jr. Drug induced hypoglycemia and hypothermia. J Maine Med Assoc 1976;67:272, 279.

36. Bruining HA, Boelhouwer RU. Acute transient hypokalemia and body temperature. Lancet 1982;2:1283-1284.

37. Koht A, Cane R, Cerullo LJ. Serum potassium levels during prolonged hypothermia. Intensive Care Med 1983;9:275-277.

38. Zydlewski AW, Hasbargen JA. Hypothermia-induced hypokalemia. Mil Med 1998;163:719-721.

39. Wladis A, Hjelmqvist H, Brismar B, et al. Acute metabolic and endocrine effects of induced hypothermia in hemorrhagic shock: an experimental study in the pig. J Trauma 1998;45:527-533.

40. Schubert A. Side effects of mild hypothermia. J Neurosurg Anesthesiol 1995;7:139-147.

41. Valeri CR, Feingold H, Cassidy G, et al. Hypothermia-induced reversible platelet dysfunction. Ann Surg 1987;205:175-181.

42. Oung CM, Li MS, Shum-Tim D, et al. In vivo study of bleeding time and arterial hemorrhage in hypothermic versus normothermic animals. J Trauma 1993;35:251-254.

43. Broman M, Kallskog O, Nygren K, et al. The role of antidiuretic hormone in cold-induced diuresis in the anaesthetized rat. Acta Physiol Scand 1998;162:475-480.

44. Chen RY, Chien S. Hemodynamic functions and blood viscosity in surface hypothermia. Am J Physiol 1978;235:H136-143.

45. Debakey ME, Morris G, Moyer JH. Hypothermia. I. Effect on renal hemodynamics and on excretion of water and electrolytes in dog and man. Ann Surg 1957;145:26-40.

46. Moyer JH, Heider C, Morris GC Jr, et al. Hypothermia. III. The effect of hypothermia on renal damage resulting from ischemia. Ann Surg 1957;146:152-166.

47. Michenfelder JD, Theye RA. Hypothermia: effect on canine brain and whole-body metabolism. Anesthesiology 1968;29:1107-1112.

48. Weinrauch V, Safar P, Tisherman S, et al. Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs. Stroke 1992;23:1454-1462.

49. Yoshida M, Shibata K, Itoh H, et al. Cardiovascular responses to the induction of mild hypothermia in the presence of epidural anesthesia. Anesthesiology 2001; 94:678-682.

50. Cabell LW, Perkowski SZ, Gregor T, et al. The effects of active peripheral skin warming on perioperative hypothermia in dogs. Vet Surg 1997;26:79-85.

51. Van Oss CJ, Absolom DR, Moore LL, et al. Effect of temperature of the chemotaxis, phagocytic engulfment, digestion and O2 consumption of human polymorphonuclear leukocytes. J Reticuloendothel Soc 1980;27:561-565.

52. Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med 1996;334:1209-1215.

53. Beal MW, Brown DC, Shofer FS. The effects of perioperative hypothermia and the duration of anesthesia on postoperative wound infection rate in clean wounds: a retrospective study. Vet Surg 2000;29:123-127.

54. Gyulai FE. Anesthetics and cerebral metabolism. Curr Opin Anaesthesiol 2004;17:397-402.

55. Brunner EA, Cheng SC, Berman ML. Effects of anesthesia on intermediary metabolism. Annu Rev Med 1975;26:391-401, 1975.

56. Drummond GB. Reduction of tonic ribcage muscle activity by anesthesia with thiopental. Anesthesiology 1987;67:695-700.

57. Haskins S. Perioperative monitoring. In: Paddleford R, ed. Manual of small animal anesthesia. 2nd ed. Philadelphia, Pa: WB Saunders Co, 1999;123-146.

58. Rutherford EJ, Fusco MA, Nunn CR, et al. Hypothermia in critically ill trauma patients. Injury 1998;29:605-608.

59. Jurkovich GJ, Greiser WB, Luterman A, et al. Hypothermia in trauma victims: an ominous predictor of survival. J Trauma 1987;27:1019-1024.

60. Steinemann S, Shackford SR, Davis JW. Implications of admission hypothermia in trauma patients. J Trauma 1990;30:200-202.

61. Sori AJ, el-Assuooty A, Rush BF Jr, et al. The effect of temperature on survival in hemorrhagic shock. Am Surg 1987;53:706-710.