CLINICAL STUDY Indian Journal of Clinical Practice, Vol. 30, No. 5, October 2019 Clinical Efficacy of Mannitol 10% with Glycerol 10% versus Mannitol 20% in Cerebral Edema AVINASH SHANKAR*, SHUBHAM†, AMRESH SHANKAR‡, ANURADHA SHANKAR# ABSTRACT Introduction: Cerebral edema is a common cause of unconsciousness and a manifestation in cerebrovascular accident, head injury, convulsive disorder and encephalitis, either due to infection or toxin. Failure of energy-dependent sodium-potassium ATPase pump, results in accumulation of sodium and water. The release of free radicals and proteases due to activation of microglial cells disrupts cell membrane and capillaries. Objective of the study: Comparative assessment of clinical efficacy of mannitol 10% with glycerol 10% versus mannitol 20% in cerebral edema of varied origin. Material and methods: In this study, 1171 patients of cerebral edema of various etiology attending Medical Emergency of RA Hospital & Research Centre, Warisaliganj (Nawada), Bihar, were selected for comparative evaluation of mannitol 10% with glycerol 10% versus mannitol 20% intravenously to adjudge the clinical efficacy and safety profile. Results: Patients of Group A taking mannitol 10% with glycerol 10% had Grade I clinical response in 584/586 without any adversity, residual neurological deficit or mortality and morbidity while among patients of Group B on mannitol 20%, only 108/585 had Grade I clinical response with mortality in 92 cases and morbidity in 279 cases. Keywords: Cerebral edema, cerebrovascular accident, sodium potassium ATPase pump, free radicals, proteases, mortality, morbidity erebral edema is a common sequel of causes dysfunction but not necessarily permanent cerebrovascular accident (CVA), head injury, damage. Ultimately, hypoxia depletes the cells’ energy Cconvulsive disorder and infective or toxic stores and disables the sodium-potassium ATPase, involvement of brain. Cerebral edema pathogenesis reducing calcium exchange. at cellular level is complex as - damaged cells swell, Failure of the energy-dependent sodium pump in the injured blood vessels leak and blocked absorption cellular membrane causes accumulation of sodium and pathways force fluid to enter brain tissues. Cellular water into the intracellular space to maintain osmotic and blood vessel damage follows an injury cascade, i.e., gradient while accumulation of calcium inside the cell release of glutamate into the extracellular space opens activates intracellular cytotoxic processes. Formation calcium and sodium entry channels on cell membranes. of genes like c-foc and c-jun and cytokines and other Membrane ATPase pump releases one calcium ion in intermediary substances initiate inflammatory response. exchange for 3 sodium ions which creates an osmotic gradient promoting increased water entry to cells and Activation of microglial cells releases free radicals and proteases that attack cell membranes and capillaries, which results in the cell recovery impossible. In addition, due to negligent and lack of proper *Chairman, National Institute of Health & Research restrictions, investigations and health care counseling Institute of Applied Endocrinology and education, people suffer from dreaded sequel of Warisaliganj (Nawada), Bihar †Consultant Pediatrician, Delhi hypertension, i.e., CVA resulting in unconsciousness, ‡Hon Director, Aarogyam Punarjeevan, Patna, Bihar convulsion, paralysis and coma, which modify the #Senior Research Fellow Regional Institute of Ayurveda, Itanagar, Arunachal Pradesh outcome of the disease and increase the mortality. Address for correspondence Dr Avinash Shankar To overcome brain edema, the commonly prescribed Chairman, National Institute of Health & Research urgent measure remains intravenous mannitol and Institute of Applied Endocrinology Warisaliganj (Nawada), Bihar - 805 130 oxygen inhalation. Usually oral glycerol is also the E-mail: [email protected] choice to relieve brain edema. 452 IJCP SUTRA: "Patients with pulmonary TB should be monitored by follow-up sputum microscopy at defined intervals." Indian Journal of Clinical Practice, Vol. 30, No. 5, October 2019 CLINICAL STUDY Considering the clinical effect of oral glycerol and  Specific treatment (antihypertensive measure for availability of mannitol 10% with glycerol 10%, a clinical hypertension, antidiabetic measure for diabetes study was conducted to evaluate the clinical effect and mellitus) safety profile of 10% glycerol with 10% mannitol versus  IV nutrition mannitol 20% in the management of cerebral edema of  IV chemoprophylaxis varied origin.  Other desired measures as per need OBJECTIVE OF THE STUDY (anticonvulsant for convulsion) To adjudge the clinical efficacy of mannitol 10% with  Diazepam administration was duly restricted. glycerol 10% versus mannitol 20% in the management While Group A patients were given mannitol 10% and of cerebral edema of varied origin. glycerol 10% (Glycerol is a potent osmotic dehydrating agent with additional effects on brain metabolism in STUDY DESIGN doses of 0.25-2.0 g/kg glycerol) intravenous, Group B received mannitol 20%. Mannitol in a dose of 1.5 g/kg This was a comparative clinical study. body weight was infused over a period of 15 minutes, MATERIAL AND METHODS followed by 0.5 g/kg body weight every 8 hours until the patient regained consciousness or for a maximum Material period of 72 hours. Patients were assessed as per following index of Overall, 1171 patients of cerebral edema of varied origin assessment: attending RA Hospital & Research Centre Emergency were selected for evaluation of mannitol 10% with  Recovery time from unconsciousness glycerol 10% versus conventional mannitol 20% therapy.  Status of paralysis Methods  Neural recovery z Status of alertness Parents or attendants of the admitted patients were thoroughly interrogated for the presenting feature z Status of speech onset, its duration, treatment taken and its outcome, z Mental capability any history of such attacks in past. All the patients were z Motor power and tone examined for their blood pressure, temperature, any marks of injury over the head, blood sugar and samples  Effect on various bio-parameters were collected for other vital parameters assessment.  Post-therapy sequel: Patients were classified into two groups comprising z Polyuria equal number of patients (Table 1). z Polydipsia All the patients, irrespective of their cause of z Irritability unconsciousness or cerebral edema, were advocated: z Pulmonary congestion  Oxygen inhalation z Fluid and electrolyte imbalance Table 1. Distribution of Patients on the basis of Clinical z Acidosis Status z Electrolyte loss Clinical status Group A Group B z Dryness of mouth, thirst Head injury 54 54 z Marked diuresis Cerebrovascular accident 315 315 z Urinary retention z Toxemia 5 5 Edema z Headache Febrile convulsion 5 5 z Blurred vision Convulsive disorder 181 180 z Convulsions Encephalitis 26 26 z Nausea IJCP SUTRA: "TB patients living with HIV should receive the same duration of TB treatment with daily regimen." 453 CLINICAL STUDY Indian Journal of Clinical Practice, Vol. 30, No. 5, October 2019 z Vomiting Table 2. Number of Patients of Cerebral Edema z Hypotension Age group Number of patients z Tachycardia (years) Male Female Total To assess the safety profile of the administered drug, the basic bio-parameters, i.e., hematological, hepatic 10-15 09 05 14 and renal profile, were repeated. 15-20 11 07 18 On the basis of clinical achievement, clinical response 20-25 28 13 41 was graded as: 25-30 64 34 98 Grade I: Complete recovery from unconsciousness 30-35 58 26 84 within 6 hours. No convulsion, Recovery from paralysis (motor power and tone) without any adversity and 35-40 87 29 116 residual neuropsychiatric presentation or change in bio- 40-45 54 24 78 parameters. 45-50 58 30 88 Grade II: Complete recovery from unconsciousness within 12 hours. No convulsion, Recovery from 50-55 110 54 164 paralysis (motor power and tone) without any adversity 55-60 130 70 200 and residual neuropsychiatric presentation or change in bio-parameters >60 188 82 270 Grade III: Improvement in unconsciousness, complete Total 797 (68%) 374 (32%) 1,171 recovery in >48 hours. Occasional convulsion, improvement in power and tone, presence of adversity like polyuria, polydipsia, hypotension, tachycardia, Male Female blurred vision, post-therapy urinary retention, marked change in bio-parameters. OBSERVATION AND RESULTS Among the admitted 1,171 patients of cerebral edema, 374 797 (68%) and 374 (32%) were male and female, respectively. Majority of the patients were of age >50 years, though 14 cases were in the age group of 10-15 years (Table 2 and Fig. 1). Out of all, majority had CVA (630 [53.8%]), 361 (30.8%) 797 had convulsive disorder while 108 (9.2%) had head injury (Table 3). Among the selected patients, 77.2% were hypertensive, out of which 9.3% had malignant hypertension (average >160) (Table 4); 75.5% were diabetic, out of which 10.7% had random blood sugar >400 mg% Figure 1. Pie diagram showing sex-wise distribution of (Table 5). patients. All admitted cases were unconscious, 36.9% presented Among the selected patients, 183 were addicted to all with convulsion and 53.8% with hemiplegia (Table 6). types of narcotics while 355 were having no history of In all, 67.3% patients had been admitted within any personal habits (Table 8); 865 were pure vegetarian 24 hours of incident while the rest after 24 hours while rest were nonvegetarian (Fig. 3). (Fig. 2). Of all the patients, 704 known