Electrolyte & Blood Pressure :, 00 ) Mannitolinduced Metabolic Alkalosis Kyung Pyo Kang, M.D., Sik Lee, M.D., Kyung Hoon Lee, M.D., and Sung Kyew Kang, M.D. Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Chonbuk, Korea Mannitol is an osmotic diuretic agent useful in a variety of clinical conditions. This study is based on acidbase and electrolyte changes seen after the intravenous infusion of hypertonic mannitol for the prevention of cerebral edema. The study subjects were divided into groups: for group A, an amount of 00900 ml % mannitol was intravenously infused over the period of 0 to 90 minutes; for group B,,00,00 ml over to hours; and for group C,,00,900 ml over more than hours. In group A, blood ph is increased from.±0.0 to.±0.0, and plasma HCO from.±. to.9±.9 meq/l, but plasma K + is decreased from ±0. to.±0. meq/l. In group B, blood ph is increased from ±0.0 to.±0.0, and plasma HCO from.±. to 9.±.9 meq/l, but plasma K + is decreased from ±0. to.± meq/l. In group C, blood ph is increased from ±0.0 to.±0.0, and plasma HCO from.9±. to.±. meq/l, but plasma K + is decreased from ±0. to.9±0. meq/l. These results showed that intravenous infusion of mannitol could induce metabolic alkalosis and hypokalemia, regardless of its dose. The mannitol induced metabolic alkalosis may be due to increased renal HCO production. Key Words : Mannitol, Metabolic alkalosis Introduction Metabolic alkalosis is a primary acidbase disturbance manifested as an elevated arterial ph and increased PaCO due to alveolar hypoventilation. A retrospective study of arterial blood gases in hospitalized patients showed that metabolic alkalemia was the most common acidbase disturbances, occurring in % of the abnormal cases ). Metabolic alkalosis may occur due to elevated plasma HCO concentration that is usually induced by H + loss from the gastrointestinal tract (i.e. vomiting or nasogastric suction) or from the kidney (i.e. diuretic therapy). Metabolic alkalosis may also be produced in bicarbonate retention, hydrogen ion movement into the cells, or in certain forms of volume Correspondence author : Sung Kyew Kang, M.D. Department of Internal Medicine, Chonbuk National University Medical School, Korea Tel : 0)0, Fax : 0)09 Email : hope@chonbuk.ac.kr contraction ). In both medical and surgical patients, alkalemia is most likely to occur in patients who are sicker and have had a complicated hospital course. The mortality rate among medical patients exceeded that of surgical patients when the ph level was greater than.. There was an inverse correlation between the ph value and the prognosis ). Mannitol is a carbon alcohol with a molecular weight of. For being an obligatory solute, mannitol may be used either as an osmotic diuretics to maintain water excretion, or to reduce the cerebral edema or intracranial pressure in cerebrovascular disease; a rapid infusion of 0% mannitol solution has been widely used ). Although various studies on the effectiveness of mannitol have been performed, there are few reports on acidbase disorder in Korea. This study is based on acidbase and electrolyte changes seen after the intravenous infusion of hypertonic mannitol was given for the prevention of cerebral edema.
KP Kang : Mannitolinduced Metabolic Alkalosis Materials and Methods The patients, who were hospitalized at Chonbuk National University Hospital for the symptoms and signs of cerebral hemorrhage from January 00 through December 00, were enrolled in this study. The diagnosis of cerebral hemorrhage was made based on the characteristic symptoms (e.g., headache, vomiting, hemiparesis etc.), and focal neurologic signs. In some cases the diagnosis of cerebral hemorrhage was documented by brain computed tomography. Among patients, patients were diagnosed as acute subdural hematoma, as intracranial hematoma, and as subarachnoid hemorrhage.. Study protocol The study was a retrospective, open labeled controlled trial. Patients were randomly assigned to various amounts of % mannitol to be administered. A had 00900 ml of % mannitol infused over 0 to 90 minutes. B had,0000 ml over to hours. C had,00,900 ml over more than hours. Arterial blood samples for arterial blood gas analysis (Nova biotech; El Cajon, CA, USA) were obtained. The serum electrolytes, BUN and creatinine were also measured by ASTRA (Beckman; Fullerton, CA, USA). The serum and urine osmolality were measured by osmometer (Advanced; Norwood, MA, USA).. Statistics All data were expressed by mean±standard deviation. Comparisons of data were performed by using paired student ttest. p<0.0 is considered significant. Results. Patients There were patients enrolled for the study and patients' profiles were described in Table. There were male and 0 female patients.. Acidbase and electrolyte changes after the infusion of % mannitol over the period of 0 to 90 minutes A, consisted of patients, were infused with 00900 ml of the % mannitol over the period of 0 to 90 minutes. The baseline mean blood ph was.±0.0. At 90 minutes after % mannitol infusion, blood ph increased significantly to.±0.0; The serum HCO increased significantly from.±. meq/l to.9±0. meq/l; Serum potassium level decreased significantly from ±0. meq/l to.±0. meq/l; Serum creatinine level decreased from ±0. mg/dl to ±0. mg/dl. The changes seen in creatinine level may be due to an increased glomerular filtration rate (Table ).. Acidbase and electrolyte changes after the infusion of % mannitol over the period of to hours B, consisted of 9 patients, were infused with,00,00 ml of the % mannitol over the period of to hours. Blood ph, serum HCO, serum potassium, and serum creatinine level at the baseline and after % mannitol infusion were following: blood ph (±0.0 versus.±0.0), serum HCO (.±. versus 9.±.9 meq/l), serum potassium (±0. versus.± meq/l), serum creatinine (±0. versus ±0. mg/dl) (Table ). The values showed significant difference before and after % mannitol infusion. Decreased creatinine level may be due to the change in the glomerular filtration rate. Table. Patients Characteristics Number of cases Gender (M/F) (yrs)(mean) ASH ICH SAH / () / 0() / 0() Abbreviations : ASH, acute subdural hematoma; ICH, Intracerebral hematoma, SAH: Subarachnoid hemorrhage
KP Kang : Mannitolinduced Metabolic Alkalosis Table. Blood Acidbase and Electrolyte Parameters (mean±se) after % Mannitol Infusion for 090 Minutes ph PCO HCO Na K Cl Cr Osm ph PCO HCO Na K Cl Cr Osm /M 0/M /F 0/M /M /F /M /F..0.9.0.0.. 0. 9. 0.. 9.9.... 9.9... 0 00 0 0 09... 0 9 9.9......... 9. 0. 0. 0.0 9. 0. 0...9..0..9..9. 9 9 0 0 0 0. 0. 0.. 0. 0 mean ±SE. ±0.0 9. ±. ±..9 ±. ±0. 0.0 ±. ±0. ±.. ±0.0 0. ±.0.9 ±.9 9. ±. 0. ±0. ± ±0. ± PCO, arterial CO partial pressure; HCO, bicarbonate; Na, sodium; K, potassium; Cl, chloride; Cr, creatinine; Osm, osmolality; M, male; F, female, p<0.0, Table. Blood Acidbase and Electrolyte Parameters (mean±se) after % Mannitol Infusion for Hours (group B) ph PCO HCO Na K Cl Cr ph PCO HCO Na K Cl Cr 9 /M /F 9/M /M /F /M /F 0/F /F. 9..0 0.0.... 9.0...... 9. 9 9.9.... 0 0 0 0 0 09............9.. 9....9..0. 9.... 9.. 9..9.... 9 00 9 0 0 0. 0. mean ±SE ±0.0. ±.. ±.. ±. ±0. 0. ±0. ±0.. ±0.0 0. ±. 9.. ±.9 ±0.. 0 ± ±. ±0. PCO, arterial CO partial pressure; HCO, bicarbonate; Na, sodium; K, potassium; Cl, chloride; Cr, creatinine; Osm, osmolality; M, male; F, female; p<0.0,. Acidbase and electrolyte changes after infusion of % mannitol over more than hour period C, consisted of patients, were infused with % mannitol over more than hour period. Total amount of infused mannitol was,00 to,900 ml. The mean blood ph was ±0.0. After the % mannitol infusion, the blood ph increased to.±0.0. Serum HCO increased from.9±. meq/l to.±. meq/l. Serum potassium level decreased from ±0. meq/l to.9 meq/l. Serum creatinine decreased from.±0. mg/dl to.± mg/dl, which may be due to increased glomerular filtration rate (Table ). Discussion Intravenous infusion of % mannitol may increase the blood ph and serum HCO, and decrease the serum potassium and creatinine levels. Metabolic alkalosis may occur due to increased renal HCO production after mannitol infusion ). Increased GFR after mannitol infusion may increase the distal tubular Na+ loading and proximal tubular HCO reabsorption. This phenomenon, in turn, may increase renal HCO pro
KP Kang : Mannitolinduced Metabolic Alkalosis Table. Blood Acidbase and Electrolyte Parameters (mean±se) after % Mannitol Infusion for Hours (group C) ph PCO HCO Na K Cl Cr ph PCO HCO Na K Cl Cr Uvol 0/F 9/F /M /F.9. 0. 0.....9. 09 0 0...........9. 9.9.. 0 0.. 0.,90,00,0,00 meanse ±0.0. ±..9 ±.. ±. ±0. 09.0 ±.9. ±0.. ±0.0. ±... ±. ±..9 0 ±0. ±.. ±,00 PCO, arterial CO partial pressure; HCO, bicarbonate; Na, sodium; K, potassium; Cl, chloride; Cr, creatinine; Osm, osmolality; M, male; F, female; p<0.0, Blood ph... Plasma K + (meq/l). 0 Fig.. Changes of blood ph before and after % mannitol infusion for 090 minutes (A group), hours (B group) and over hours (C group). p< 0.0, Plasma HCO (meq/l) 0 0 0 0 Fig.. Changes of plasma HCO concentration before and after % mannitol infusion for 090 minutes (A group), hours (B group) and over hours (C group). p<0.0, differing from the baseline values duction, and cause metabolic alkalosis. Osmotic diuretics are obligate solutes of low molecular weight, and are freely filtered at the glomerulus Fig.. Changes of plasma potassium concentration before and after % mannitol infusion for 090 minutes (A group), hours (B group) and over hours (C group). p<0.0, differing from the baseline values. Serum Cr (mg/dl)..0. 0.0 Fig.. Changes of serum creatinine concentration before and after % mannitol infusion for 090 minutes (A group), hours (B group) and over hours (C group). p<0.0, differing from the baseline values and poorly reabsorbed by the renal tubules. The osmotic effect of mannitol depresses proximal reabsorption of water more than sodium, thereby decreasing proximal tubular sodium concentration. The
KP Kang : Mannitolinduced Metabolic Alkalosis natriuretic effect of mannitol results from decreased sodium reaborption in the loop of Henle ). Intravenous infusion of hypertonic solution of mannitol has been shown to be effective in lowering intracranial pressure and decreasing the mass of brain, as well as lowering intraocular pressure ). Upon infusion of hypertonic mannitol ( to. g/kg in to 90 H + K + ATPase and H + ATPase pump, and may have an effect on distal hydrogen secretion. In summary, these results showed that intravenous infusion of mannitol could induce metabolic alkalosis and hypokalemia, regardless of its dose. The mannitol induced alkalosis may be caused by increased renal HCO production. minutes), osmolarity of serum was increased from to mosm/l), and the osmotic gradient between References cerebrospinal fluid and serum was to mosm/l ). The decreased cerebrospinal fluid pressure is due to the movement of water from the brain into extracellular fluid. The movement of water out of the brain in response to the osmotic effect of mannitol decompresses the brain when cerebral edema is present ). Metabolic alkalosis may be produced by elevated plasma HCO concentration and decreased renal HCO excretion in the urine. In this study, hypokalemia occurred after mannitol infusion. Decreased serum potassium level may cause increased proximal tubular HCO reabsorption and distal tubular H + secretion. Hypokalemia and aldosterone stimulate the ) Hodgkin JE, Soeprono FF, Chan DM : Incidence of metabolic alkalemia in hospitalized patients. Crit Care Med :, 90 ) Rose BD, Post TW : Metabolic alkalosis. In: Clinical physiology of acidbase and electrolyte disorders th ed., International Edition. Singapore, McGrawHill, 00, p ) Anderson LE, Henrich WL : Alkalemiaassociated morbidity and mortality in medical and surgical patients. South Med J 0:9, 9 ) Nissenson AR, Weston RE, Kleeman CR. Mannitol. West J Med :, 99. ) Wise BL : Effects of infusion of hypertonic mannitol on electrolyte balance and osmolarity of serum and cerebrospinal fluid. J Neurosurg 0:99, 9