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Table of Contents
REVIEW
Year : 2018  |  Volume : 7  |  Issue : 4  |  Page : 149-151

Pharmacological potential of acetazolamide in traumatic intracranial hypertension


1 University of Cartagena, Cartagena de Índias, Bolivar; Center for Biomedical Research, Faculty of Medicine-University of Cartagena, Cartagena, Colombia
2 University of Cartagena, Cartagena de Índias, Bolivar; Cartagena Neurotrauma Research Group, Universidad de Cartagena, Cartagena, Colombia
3 Cartagena Neurotrauma Research Group, Universidad de Cartagena; Coordinator Center for Biomedical Research (CIB), Faculty of Medicine - University of Cartagena, Cartagena, Colombia
4 Department of Neurosurgery, Neurosurgery teaching Hospital-Baghdad, Iraq
5 Center for Biomedical Research, Faculty of Medicine-University of Cartagena, Cartagena; Cartagena Neurotrauma Research Group, Universidad de Cartagena; Specialist in Neurosurgery, Faculty of Medicine - University of Cartagena, Cartagena de Indias, Bolívar, Colombia

Date of Submission27-Jul-2018
Date of Decision14-Aug-2018
Date of Acceptance20-Aug-2018
Date of Web Publication12-Sep-2018

Correspondence Address:
Luis Rafael Moscote-Salazar
Center for Biomedical Research (CIB), Faculty of Medicine - University of Cartagena
Colombia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2221-6189.241015

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  Abstract 


Traumatic brain injuries are an important cause of morbidity and mortality around the world. These types of lesions are often associated with increased intracranial pressure and cerebral edema, proper management of this can reduce tissue damage of the brain and improve brain perfusion. The use of acetazolamide is not indicated in guidelines for the management of intracranial hypertension, which is used to a great extent for the management of idiopathic intracranial hypertension. However, it is not yet known in the management of traumatic intracranial hypertension.

Keywords: Brain injuries, Intracranial hypertension, Acetazolamide


How to cite this article:
Daniela LC, Yancarlos RV, Huber S P, Andrea AL, Loraine QP, Hugo CS, Hoz SS, Moscote-Salazar LR. Pharmacological potential of acetazolamide in traumatic intracranial hypertension. J Acute Dis 2018;7:149-51

How to cite this URL:
Daniela LC, Yancarlos RV, Huber S P, Andrea AL, Loraine QP, Hugo CS, Hoz SS, Moscote-Salazar LR. Pharmacological potential of acetazolamide in traumatic intracranial hypertension. J Acute Dis [serial online] 2018 [cited 2022 Oct 3];7:149-51. Available from: https://www.jadweb.org/text.asp?2018/7/4/149/241015




  1. Introduction Top


Brain trauma represents an important source of morbidity and mortality in the world. About 10 million people in the world die or are hospitalized as a result of this. Its etiology is varied and depends on variables such as age, place of residence, sex, socioeconomic stratum, among others; For example, in young people, the most common causes are car accidents and assaults. Subsequent to a traumatic injury, the risk of developing intracranial hypertension and cerebral ischemia increases[1],[2].

Acetazolamide is a drug that helps to reduce cerebrospinal fluid secretion. However, it is not recommended for this type of lesions, but in idiopathic intracranial hypertension. (3-6) This article aims to describe the pathophysiology of traumatic intracranial hypertension and the mechanism of action of acetazolamide, aiming to show its possible use cases of traumatic intracranial hypertension.


  2. Pathophysiology Top


Intracranial pressure (PIC), is the pressure exerted by the brain, blood and cerebrospinal fluid (CSF) in the vault of the skull. This varies with age, normal values in adults are <10-15 mmHg, in children between 9 and 11 years is 3 to 7 mmHg and in infants is 1.5-6.0 mmHg. When ICP is between 20 and 25 mmHg, treatment is required in most circumstances and values greater than 40 mmHg indicate severity, which threatens the patient’s life[3].

A closed cranial trauma is composed of two related pathological processes: the primary lesion, which has a mass effect associated with neurological dysfunction and secondary cerebral edema, and consequently the increase of ICP. Secondary lesion occurs when cerebral edema and dysregulation of blood flow result in increased ICP and cerebral ischemia. According to the Monroe-Kellie hypothesis, the intracranial space has a fixed volume given by brain tissue, blood, and CSF, so when the brain compensation mechanisms are overwhelmed due to the mass effect produced by intracranial hemorrhage and Dysfunctional edema lead to an increase in ICP[2],[3],[4]. Initially, cell death occurring at the site of injury releases excitatory amino acids such as aspartate and glutamate. This together with the activation of voltage-dependent channels of Ca2+ and Na2+ lead to apoptosis, thus causing oxidative stress, hypoperfusion, and vasospasm, leading to cerebral ischemia and edema[2].


  3. Mechanism of action of acetazolamide Top


Acetazolamide AZ is a potent inhibitor of the enzyme carbonic anhydrase[3],[5],[6],[7],[8],[9],[10] known to lower extracellular pH in the brain by inhibiting the reversible hydration of CO2 to bicarbonate ions and catalyzed protons by the same enzyme[7],[10], this occurs after the alkalization of the interior of the cells[9], in addition, it reduces the production of CSF and is used in the treatment of hydrocephalus, high altitude disease[3],[11],[12],[13] and Benign or idiopathic intracranial hypertension[3],[5],[6],[11]. However, it has other uses such as increased activity dependent on alkaline transients, decreases the power of oscillatory wave θ in REM sleep, is anticonvulsive[7],[10],[13], impairs spatial learning and can also eliminate depolarizations mediated by HCO3-dependent GABAA in rats. In addition, it has been reported that it can increase the number of triggered action potentials and depolarize the neurons, affecting brain neuronal excitability[10]. Cerebral blood flow may also vary depending on the dose of AZ used by the decrease in extracellular pH in the brain generating acid vasodilation that does not depend on AZ but from the general systemic reaction to the decrease in pH[10],[14].

AZ is the drug most commonly used to reduce ICP, mainly in idiopathic intracranial hypertension[3],[5],[6],[11]. This exerts an inhibitory action on the choroid plexus, where the active transport of Na+ ions in the cerebral ventricles by Na+ / K+ ATPase is the main driving force for CSF secretion[11].

Among the adverse effects of AZ are electrolytic disorders, hepatic enzyme alteration, renal lithiasis[15] metabolic acidosis[8],[9],[13],[15], renal failure, anorexia, vomiting, increased diuresis, Central nervous system[9], hypokalemia[8],[13], numbness of the extremities [8],[11],[13], headache, tinnitus and gastrointestinal disorders[8],[13].


  4. Management of traumatic intracranial hypertension Top


After the initial stabilization of the patient, the hemodynamic, respiratory and nutritional aspects of the patient should be optimized. For this reason, fluid administration, mechanical ventilation, and enteral feeding are necessary for this type of injury[1],[4],[11].

In order to manage the increase of ICP in cases of cerebral trauma, the main objective is to identify the underlying cause and treat it by adding the necessary measures to reduce ICP[3]. Initially, the state in which air life, breathing, and circulation are to be evaluated and treated. Then, PaCO2 can be reduced to a range between 30 and 35 mmHg, which is effective in reducing ICP. In the pharmacological treatment, hypertonic fluids, osmotic diuretics, barbiturates, among others[1],[4],[11] are used.

At the time of a brain trauma, the PIC can be elevated by the deregulation of the compensatory mechanisms of the brain. The priority in these cases is to stabilize the patient in a timely and effective manner. AZ is one of the drugs most used in the treatment of patients with idiopathic cranial hypertension. Further studies are needed to determine the potential use of this drug for the management of traumatic cranial hypertension.

Conflict of interest statement

We declare that we have no conflict of interest.



 
  References Top

1.
Alnemari AM, Krafcik BM, Mansour TR, Gaudin D. A Comparison of pharmacologic therapeutic agents used for the reduction of intracranial pressure after traumatic brain injury. World Neurosurg 2017; 106: 509-528.  Back to cited text no. 1
    
2.
Bach L, Dries DJ. Management of Traumatic Intracranial Hypertension: Old Questions With New Answers. Air Med J 2017; 36(4):156-159.  Back to cited text no. 2
    
3.
Sankhyan N, Raju KNV, Sharma S, Gulati S. Management of raised intracranial pressure. Indian J Pediatr 2010; 77(12): 1409-1416.  Back to cited text no. 3
    
4.
Goh J, Gupta AK. The management of head injury and intracranial pressure. Current 2002;13(3): 129-137.  Back to cited text no. 4
    
5.
Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. J Appl Physiol 2007; 102(4): 1313-1322.  Back to cited text no. 5
    
6.
Thurtell MJ, Wall M. Idiopathic intracranial hypertension (Pseudotumor cerebri): Recognition, treatment, and ongoing management. Curr Treat Options Neurol 2013; 15(1): 1-12.  Back to cited text no. 6
    
7.
Yamauchi H, Okazawa H, Kishibe Y, Sugimoto K, Takahashi M. The effect of acetazolamide on the changes of cerebral blood flow and oxygen metabolism during visual stimulation. Neuroimage 2003; 20(1): 543-549.  Back to cited text no. 7
    
8.
Ogasawara K, Tomitsuka N, Kobayashi M, Komoribayashi N, Fukuda T, Saitoh H, et al. Stevens-Johnson syndrome associated with intravenous acetazolamide administration for evaluation of cerebrovascular reactivity. Case report. Neurol Med Chir (Tokyo) 2006; 46: 161-163.  Back to cited text no. 8
    
9.
Hathout RMRM, Mansour S, Mortada NDND, Guinedi ASAS. Liposomes as an ocular delivery system for acetazolamide: Ín vitro and in vivo studies. AAPS PharmSciTech 2007; 5(8): 1.  Back to cited text no. 9
    
10.
Aamand R, Skewes J, Møller A, Fago A, Roepstorff A. Enhancing effects of acetazolamide on neuronal activity correlate with enhanced visual processing ability in humans. Neuropharmacology 2011; 61(5-6): 900-908.  Back to cited text no. 10
    
11.
Uldall M, Botfield H, Jansen-Olesen I, Sinclair A, Jensen R. Acetazolamide lowers intracranial pressure and modulates the cerebrospinal fluid secretion pathway in healthy rats. Neurosci Lett 2017; 645: 33-39.  Back to cited text no. 11
    
12.
Tricarico D, Barbieri M, Camerino DC. Acetazolamide opens the muscular K(Ca2+) channel: A novel mechanism of action that may explain the therapeutic effect of the drug in hypokalemic periodic paralysis. Ann Neurol 2000; 48(3): 304-312.  Back to cited text no. 12
    
13.
Saito H, Ogasawara K, Suzuki T, Kuroda H, Kobayashi M, Yoshida K, et al. Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion singlephoton emission computed tomography in patients with major cerebral artery steno-occlusive diseases. Neurol Med Chir (Tokyo) 2011; 51: 479-483.  Back to cited text no. 13
    
14.
Vanninen E, Kuikka JT, Tenhunen-Eskelinen M, Vanninen R, Mussalo H. Haemodynamic effects of acetazolamide in patients with cardiovascular disorders: Correlation with calculated cerebral perfusion reserve. Nucl Med Commun 1996; 17: 325-330.  Back to cited text no. 14
    
15.
Jonathan C. Horton. Acetazolamide for pseudotumor cerebri: Evidence from the nordic trial. JAMA 2014; 311(16): 1618-1619.  Back to cited text no. 15
    




 

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