Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury

Restricted access

Object. Induced hypothermia in patients with severe head injury may prevent additional brain injury and improve outcome. However, this treatment is associated with severe side effects, including life-threatening cardiac tachyarrhythmias. The authors hypothesized that these arrhythmias might be caused by electrolyte disorders and therefore studied the effects of induced hypothermia on urine production and electrolyte levels in patients with severe head injury.

Methods. Urine production, urine electrolyte excretion, and plasma levels of Mg, phosphate, K, Ca, and Na were measured in 41 patients with severe head injury. Twenty-one patients (Group 1, study group) were treated using induced hypothermia and pentobarbital administration, and 20 patients (Group 2, controls) were treated with pentobarbital administration alone. In Group 1, Mg levels decreased from 0.98 ± 0.15 to 0.58 ± 0.13 mmol/L (mean ± standard deviation; p < 0.01), phosphate levels from 1.09 ± 0.19 to 0.51 ± 0.18 mmol/L (p < 0.01), Ca levels from 2.13 ± 0.25 to 1.94 ± 0.14 mmol/L (p < 0.01), and K levels from 4.2 ± 0.59 to 3.6 ± 0.7 mmol/L (p < 0.01) during the first 6 hours of cooling. Electrolyte levels in the control Group 2 remained unchanged. Electrolyte depletion in Group 1 occurred despite the fact that moderate and, in some cases, substantial doses of electrolyte supplementation were given to many patients, and supplementation doses were often increased during the cooling period. Average urine production increased during the cooling period, from 219 ± 70 to 485 ± 209 ml/hour. When the targeted core temperature of 32°C was reached, urine production returned to levels that approximated precooling levels (241 ± 102 ml/hour). Electrolyte levels rose in response to high-dose supplementation. In the control group, urine production and electrolyte excretion remained unchanged throughout the study period.

Conclusions. Induced hypothermia is associated with severe electrolyte depletion, which is at least partly due to increased urinary excretion through hypothermia-induced polyuria. This may be the mechanism through which induced hypothermia can lead to arrhythmias. When using this promising new treatment in patients with severe head injury, stroke, or postanoxic coma following cardiopulmonary resuscitation, prophylactic electrolyte supplementation should be considered and electrolyte levels should be monitored frequently.

Article Information

Address reprint requests to: Kees H. Polderman, M.D., Ph.D., Surgical Intensive Care Unit, University Hospital Vrije Universiteit, Post Office Box 7057, 1007 MB Amsterdam, The Netherlands. email: k.polderman@tip.nl.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Protocol for the treatment of patients with severe head injury. CT = computerized tomography; EEG = electroencephalography; MAP = mean arterial pressure.



Aubier MMurciano DLecocguic Yet al: Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure. N Engl J Med 313:4204241985N Engl J Med 313:


Bernard S: Induced hypothermia in intensive care medicine. Anaesth Intensive Care 24:3823881996Bernard S: Induced hypothermia in intensive care medicine. Anaesth Intensive Care 24:


Bollaert PELevy BNace Let al: Hemodynamic and metabolic effects of rapid correction of hypophosphatemia in patients with septic shock. Chest 107:169817011995Chest 107:


Brown GRGreenwood JK: Drug- and nutrition-induced hypophosphatemia: mechanisms and relevance in the critically ill. Ann Pharmacother 28:6266321994Ann Pharmacother 28:


Busto RGlobus MYTDietrich WDet al: Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 20:9049101989Stroke 20:


Chernow BBamberger SStoiko Met al: Hypomagnesemia in patients in postoperative intensive care. Chest 95:3913971989Chest 95:


Clifton GLAllen SBarrodale Pet al: A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma 10:2632731993J Neurotrauma 10:


Dempsey RJCombs DJMaley MEet al: Moderate hypothermia reduces postischemic edema development and leukotriene production. Neurosurgery 21:1771811987Neurosurgery 21:


Fisher JMagid NKallman Cet al: Respiratory illness and hypophosphatemia. Chest 83:5045081983Chest 83:


Gravelyn TRBrophy NSiegert Cet al: Hypophosphatemia-associated respiratory muscle weakness in a general inpatient population. Am J Med 84:8708761988Am J Med 84:


Hayashi NHirayama TUdagawa Aet al: Systemic management of cerebral edema based on a new concept in severe head injury patients. Acta Neurochir Suppl 60:5415431994Acta Neurochir Suppl 60:


Kaufman HHTimberlake GVoelker Jet al: Medical complications of head injury. Med Clin North Am 77:43601993Med Clin North Am 77:


Keller CWilliams A: Cardiac dysrhythmias associated with central nervous system dysfunction. J Neurosci Nurs 25:3493551993J Neurosci Nurs 25:


Knaus WADraper EAWagner DPet al: Apache II: a severity of disease classification system. Crit Care Med 13:8188291985Crit Care Med 13:


Marion DWLeonov YGinsberg Met al: Resuscitative hypothermia. Crit Care Med 24 (Suppl 2):S81S891996Crit Care Med 24 (Suppl 2):


Marion DWPenrod LEKelsey SFet al: Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med 336:5405461997N Engl J Med 336:


McIntosh TKYamakami IFaden AIet al: Magnesium protects against neurological deficit after brain injury. Brain Res 482:2522601989Brain Res 482:


Metz CHolzschuh MBein Tet al: Moderate hypothermia in patients with severe head injury: cerebral and extracerebral effects. J Neurosurg 85:5335411996J Neurosurg 85:


Milde LN: Clinical use of mild hypothermia for brain protection: a dream revisited. J Neurosurg Anesthesiol 4:2112151992Milde LN: Clinical use of mild hypothermia for brain protection: a dream revisited. J Neurosurg Anesthesiol 4:


Nadler JLRude RK: Disorders of magnesium metabolism. Endocrinol Metab Clin North Am 24:6236411995Endocrinol Metab Clin North Am 24:


Nakamura TNagao SKawai Net al: Significance of multimodal cerebral monitoring under moderate therapeutic hypothermia for severe head injury. Acta Neurochir Suppl 71:85871998Acta Neurochir Suppl 71:


Ognibene ACiniglio RGreifenstein Aet al: Ventricular tachycardia in acute myocardial infarction: the role of hypophosphatemia. South Med J 87:65691994South Med J 87:


Polderman KHBloemers FWPeerdeman SMet al: Hypomagnesemia and hypophosphatemia at admission in patients with severe head injury. Crit Care Med 28:202220252000Crit Care Med 28:


Reinert MMBullock R: Clinical trials in head injury. Neurol Res 21:3303381999Neurol Res 21:


Resnick DKMarion DWDarby JM: The effect of hypothermia on the incidence of delayed traumatic intracerebral hemorrhage. Neurosurgery 34:2522551994Neurosurgery 34:


Ritschel WAVachharajani NN: Review of electrolyte pharmacokinetics. Methods Find Exp Clin Pharmacol 14:2412541992Methods Find Exp Clin Pharmacol 14:


Rubeiz GJThill-Baharozian MHardie Det al: Association of hypomagnesemia and mortality in acutely ill medical patients. Crit Care Med 21:2032091993Crit Care Med 21:


Schwab SSchwarz SAschoff Aet al: Moderate hypothermia and brain temperature in patients with severe middle cerebral artery infarction. Acta Neurochir Suppl 71:1311341998Acta Neurochir Suppl 71:


Schwab SSchwarz SSpranger Met al: Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 29:246124661998Stroke 29:


Shiozaki TSugimoto HTaneda Met al: Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg 79:3633681993J Neurosurg 79:


Smit AJLieverse AGvan Veldhuisen Det al: Dopaminergic modulation of physiological and pathological neurohumoral activation in man. Hypertens Res 18 (Suppl 1):S107S1111995Hypertens Res 18 (Suppl 1):


Sterz FSafar PTisherman Set al: Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs. Crit Care Med 19:3793891991Crit Care Med 19:


Tateishi ASoejima YTaira Yet al: Feasibility of the titration method of mild hypothermia in severely head-injured patients with intracranial hypertension. Neurosurgery 42:106510701998Neurosurgery 42:


Teasdale GJennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81841974Lancet 2:


Tjong Tjin Joe REgeler SMVandertop WPet al: Hypothermia reduces intracranial pressure in patients with severe traumatic brain injury. Intensive Care Med 25:951999 (Abstract)Intensive Care Med 25:


Vink RMcIntosh TKDemediuk Pet al: Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma. J Biol Chem 263:7577611988J Biol Chem 263:


Weinberg AD: Hypothermia. Ann Emerg Med 22:3703771993Weinberg AD: Hypothermia. Ann Emerg Med 22:


Weinrauch VSafar PTisherman Set al: Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs. Stroke 23:145414621992Stroke 23:


Weisinger JRBellorín-Font E: Magnesium and phosphorus. Lancet 352:3913961998Lancet 352:


Cited By



All Time Past Year Past 30 Days
Abstract Views 32 32 31
Full Text Views 124 124 19
PDF Downloads 75 75 26
EPUB Downloads 0 0 0


Google Scholar