Administration Of Acetazolamide Research Articles

Biotin and Acetazolamide for Treatment of an Unusual Child With Autism Plus Lack of Nail and Hair Growth

BackgroundPatients with autism spectrum disorder and developmental delay or encephalopathy rarely demonstrate no or negligible hair and nail growth, suggesting a biotin-responsive clinical disorder. MethodsA ten-year-old girl presented with features of autism spectrum disorder, isolated headaches, and episodes of headaches and limb shaking. Her medical history revealed that her hair and nails did not grow. Administration of biotin restored her nail and hair growth and improved intellectual ability and school performance. Her episodes of headaches, single limb shaking, and loss of consciousness responded to administration of acetazolamide, and her school performance and social skills further improved. ResultsA de novo c.1091 C > T, p.T364M pathogenic variant was found in the ATP1A2 gene by whole-exome sequencing, but a genetic etiology in the biotin-responsive metabolic pathways was not identified. ConclusionsThe combination of biotin and acetazolamide treatment was successful in restoring normal mental function and school performance. Poor or no clinical nail and hair growth in any child with a developmental delay-autism spectrum disorder presentation should be considered as evidence for a biotin-responsive genetic disorder even when exome testing is negative.

Acetazolamide as Add-on Diuretic Therapy in Exacerbations of Chronic Heart Failure: a Pilot Study.

BackgroundCongestion is the main cause of morbidity in patients with heart failure. Treatment of fluid overload is often challenging in everyday clinical practice.ObjectiveThe aim of this study was to determine the diuretic effect of acetazolamide in patients with exacerbations of chronic heart failure, in addition to their stable diuretic therapy.MethodsThis was a single-center, unblinded study. Patients hospitalized with chronic heart failure exacerbations, with left ventricular ejection fraction (EF) < 50% and signs of volume overload, with a stable dose of diuretics anticipated by the attending physician over the next 4 days, were considered eligible for the study. On day 1, patients were randomized to receive acetazolamide orally, once daily (dose-adjusted to body weight) or no treatment (control group) as add-on diuretic therapy, on days 2 and 3. Diuresis, natriuresis, fluid balance, and symptoms were assessed daily, up to day 4.ResultsTwenty patients (mean ± standard deviation age 72 ± 11.6 years; 85% men; mean EF 33.8 ± 11.4%; mean N-terminal pro-B-type natriuretic peptide 8064 ± 5593 pg/mL; mean intravenous furosemide dose 105 ± 55 mg) were enrolled. Diuresis, natriuresis, fluid balance, and symptoms were stable on days 1–4 in the control group. An increase in diuresis and natriuresis, and a greater change in fluid balance after administration of acetazolamide, were observed in patients randomized to acetazolamide. On day 4, there was a significant difference in fluid balance between the acetazolamide and control groups (−666 ± 1194 mL vs. +332 ± 705 mL; p = 0.035), and dyspnea was lower in patients receiving acetazolamide (visual scale, p < 0.001; 5-point Likert scale, 1.444 vs. 2.222; p = 0.04)ConclusionsIn this pilot study, the addition of acetazolamide to the background diuretic regimen in patients with chronic heart failure exacerbations produced an additional diuretic effect and alleviation of dyspnea.

Lithium-induced NDI: acetazolamide reduces polyuria but does not improve urine concentrating ability.

Lithium is the mainstay treatment for patients with bipolar disorder, but it generally causes nephrogenic diabetes insipidus (NDI), a disorder in which the renal urine concentrating ability has become vasopressin insensitive. Li-NDI is caused by lithium uptake by collecting duct principal cells and downregulation of aquaporin-2 (AQP2) water channels, which are essential for water uptake from tubular urine. Recently, we found that the prophylactic administration of acetazolamide to mice effectively attenuated Li-NDI. To evaluate whether acetazolamide might benefit lithium-treated patients, we administered acetazolamide to mice with established Li-NDI and six patients with a lithium-induced urinary concentrating defect. In mice, acetazolamide partially reversed lithium-induced polyuria and increased urine osmolality, which, however, did not coincide with increased AQP2 abundances. In patients, acetazolamide led to the withdrawal of two patients from the study due to side effects. In the four remaining patients acetazolamide did not lead to clinically relevant changes in maximal urine osmolality. Urine output was also not affected, although none of these patients demonstrated overt lithium-induced polyuria. In three out of four patients, acetazolamide treatment increased serum creatinine levels, indicating a decreased glomerular filtration rate (GFR). Strikingly, these three patients also showed a decrease in systemic blood pressure. All together, our data reveal that acetazolamide does not improve the urinary concentrating defect caused by lithium, but it lowers the GFR, likely explaining the reduced urine output in our mice and in a recently reported patient with lithium-induced polyuria. The reduced GFR in patients prone to chronic kidney disease development, however, warrants against application of acetazolamide in Li-NDI patients without long-term (pre)clinical studies.

Nanoemulsion-based electrolyte triggered in situ gel for ocular delivery of acetazolamide

In the present work the antiglaucoma drug, acetazolamide, was formulated as an ion induced nanoemulsion-based in situ gel for ocular delivery aiming a sustained drug release and an improved therapeutic efficacy. Different acetazolamide loaded nanoemulsion formulations were prepared using peanut oil, tween 80 and/or cremophor EL as surfactant in addition to transcutol P or propylene glycol as cosurfactant. Based on physicochemical characterization, the nanoemulsion formulation containing mixed surfactants and transcutol P was selected to be incorporated into ion induced in situ gelling systems composed of gellan gum alone and in combination with xanthan gum, HPMC or carbopol. The nanoemulsion based in situ gels showed a significantly sustained drug release in comparison to the nanoemulsion. Gellan/xanthan and gellan/HPMC possessed good stability at all studied temperatures, but gellan/carbopol showed partial drug precipitation upon storage and was therefore excluded from the study. Gellan/xanthan and gellan/HPMC showed higher therapeutic efficacy and more prolonged intraocular pressure lowering effect relative to that of commercial eye drops and oral tablet. Gellan/xanthan showed superiority over gellan/HPMC in all studied parameters and is thus considered as a promising mucoadhesive nanoemulsion-based ion induced in situ gelling formula for topical administration of acetazolamide.

Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus

Rats injected with by d-phenylalanine, a carbonic anhydrase (CA) activator, enhanced spatial learning, whereas rats given acetazolamide, a CA inhibitor, exhibited impairments of fear memory consolidation. However, the related mechanisms are unclear. We investigated if CAs are involved in a non-spatial recognition memory task assessed using the object recognition test (ORT). Systemic administration of acetazolamide to male CD1 mice caused amnesia in the ORT and reduced CA activity in brain homogenates, while treatment with d-phenylalanine enhanced memory and increased CA activity. We provided also the first evidence that d-phenylalanine administration rapidly activated extracellular signal-regulated kinase (ERK) pathways, a critical step for memory formation, in the cortex and the hippocampus, two brain areas involved in memory processing. Effects elicited by d-phenylalanine were completely blunted by co-administration of acetazolamide, but not of 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate (C18), a CA inhibitor that, differently from acetazolamide, does not cross the blood brain barrier. Our results strongly suggest that brain but not peripheral CAs activation potentiates memory as a result of ERK pathway enhanced activation.

Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease or obesity-hypoventilation syndrome with metabolic alkalosis. A randomized trial

BackgroundMetabolic alkalosis (MA) inhibits respiratory drive and may delay weaning from mechanical ventilation (MV). MA is common in CO2-retainer patients that need MV. Acetazolamide (ACTZ) decreases serum bicarbonate concentration and stimulates respiratory drive. This study evaluated the effects of ACTZ on the duration of MV in patients with MA and COPD or obesity hypoventilation syndrome (OHS) intubated with acute respiratory failure. MethodsMulticenter, randomized, controlled, double-blind study, with COPD or OHS patients with MV < 72 h and initial bicarbonate >28 mmol/L and pH > 7.35. Test-treatment, ACTZ 500 mg or placebo, was daily administered if pH > 7.35 and bicarbonate >26 mmol/L. Clinical, respiratory and laboratory parameters were recorded. Results47 patients (36 men) were randomized. There were no significant differences between groups in comorbidities, baseline characteristics or arterial blood gases at inclusion. The mean difference in the duration of MV between placebo and ACTZ group was 1.3 days (95%CI, −2.1–4.8; p = 0.44). Kaplan-Meier curves showed no differences in the duration of MV (Log-Rank p = 0.41). Between-group comparison of estimated marginal means (CI 95%) during MV were, respectively: PaCO2 55 (51–59) vs 48 (47–50) mm Hg, p = 0.002; bicarbonate concentration 34 (32–35) vs 29 (28–30) mmol/L, p < 0.0001; and minute volume 9.7 (8.9–10.4) vs 10.6 (9.2–12.0) L/min, p = 0.26. There were no severe adverse effects with ACTZ administration. ConclusionsAmong patients with MA and COPD or OHS, early treatment with ACTZ did not shorten significantly the duration of MV compared with placebo. Trial registryclinical.trials.gov; NCT01499485; URL:.www.clinicaltrials.gov

Morphometric evaluation of the delayed cerebral arteries response to acetazolamide test in patients with chronic carotid artery stenosis using computed tomography angiography.

The evidence accumulates that the response to acetazolamide test is delayed on the ipsilateral side to stenosis. However, the effect of acetazolamide beyond 30 min after acetazolamide administration remains unknown. The aim of this study was to assess the diameters of anterior cerebral arteries (ACAs), middle cerebral arteries (MCAs) and posterior cerebral arteries (PCAs) before and 60 min after the acetazolamide test. Seventeen patients with carotid artery stenosis ≥ 90% on the ipsilateral side and ≤ 50% on the contralateral side were enrolled into the study. Diagnosis was based on ultrasonography examination and was confirmed using digital subtractive angiography. In all patients, two computed tomography angiography examinations were carried out; the first was performed before the acetazolamide administration, while the second one was carried out 60 min after injections. In response to the acetazolamide test: PCA diameter diminished in both ipsi- and contra-lateral side to stenosis (from 1.31 to 1.24 mm and from 1.23 to 1.15 mm, respectively), ACA and MCA decreased in the contralateral side to the stenosis (from 1.33 to 1.26 mm and from 2.75 to 2.66 mm, respectively), ACA and MCA increased in the ipsilateral side to the stenosis (from 1.29 to 1.46 mm and from 2.77 to 2.96 mm, respectively). All changes were statistically significant. There were significant differences in reactivity to acetazolamide challenge between the internal carotid artery (ICA) and vertebrobasilar circulation in patients suffering from chronic carotid artery stenosis. Within the ICA territory, ACA and MCA responses vary in the affected and not affected side.

Prophylactic Effect of Oral Acetazolamide against Intraocular Pressure Elevation after Cataract Surgery in Eyes with Glaucoma

To confirm the prophylactic effect of oral acetazolamide against increased intraocular pressure (IOP) in the period immediately after cataract surgery in eyes with primary open-angle glaucoma (POAG) and to evaluate the appropriate administration time of oral acetazolamide to prevent IOP elevation. Randomized clinical study. Ninety eyes of 90 patients with well-controlled POAG scheduled for phacoemulsification. Eyes were assigned randomly to 1 of 3 groups: (1) oral acetazolamide (500 mg) administration 1 hour preoperatively, (2) oral acetazolamide (500 mg) administration 3 hours postoperatively, or (3) no acetazolamide administration. Intraocular pressure was measured using a rebound tonometer 1 hour preoperatively, at the conclusion of surgery (adjusted in the range between 15 and 25 mmHg), and 1, 3, 5, 7, and 24 hours postoperatively. The incidence of eyes with IOP elevation more than 100% above the preoperative IOP was compared. Postoperative IOP and incidence of eyes with marked IOP elevation. Mean IOP 1 hour preoperatively and that at the conclusion of surgery did not differ significantly among groups. In all groups, mean IOP was significantly elevated from 3 to 7 hours postoperatively, and then decreased at 24 hours. At 1 and 3 hours postoperatively, mean IOP was significantly lower in the group receiving oral acetazolamide preoperatively than in the other 2 groups (postoperative administration or no administration; P ≤ 0.0031). At 5, 7, and 24 hours postoperatively, the IOP was significantly lower in both the preoperative and postoperative administration groups than in the nonadministration group (P ≤ 0.0224). Intraocular pressure elevation of more than 100% occurred in 1 eye (3.3%) in the preoperative administration group, 7 eyes (23.3%) in the postoperative administration group, and 8 eyes (26.6%) in the nonadministration group; the incidence was significantly lower in the preoperative administration group (P= 0.0459). Eyes with POAG experienced short-term IOP elevation from 3 to 7 hours after phacoemulsification. Oral acetazolamide administration 1 hour preoperatively significantly reduced the IOP elevation from 1 to 24 hours, while administration 3 hours postoperatively reduced the IOP elevation at 5 hours or more after surgery.

Acetazolamide Therapy for Metabolic Alkalosis in Pediatric Intensive Care Patients.

Patients in PICUs frequently present hypochloremic metabolic alkalosis secondary to loop diuretic treatment, especially those undergoing cardiac surgery. This study evaluates the effectiveness of acetazolamide therapy for metabolic alkalosis in PICU patients. Retrospective, observational study. A tertiary care children's hospital PICU. Children receiving at least a 2-day course of enteral acetazolamide. None. Demographic variables, diuretic treatment and doses of acetazolamide, urine output, serum electrolytes, urea and creatinine, acid-base excess, pH, and use of mechanical ventilation during treatment were collected. Patients were studied according to their pathology (postoperative cardiac surgery, decompensated heart failure, or respiratory disease). A total of 78 episodes in 58 patients were identified: 48 were carried out in cardiac postoperative patients, 22 in decompensated heart failure, and eight in respiratory patients. All patients received loop diuretics. A decrease in pH and PCO2 in the first 72 hours, a decrease in serum HCO3 (mean, 4.65 ± 4.83; p < 0.001), and an increase in anion gap values were observed. Urine output increased in cardiac postoperative patients (4.5 ± 2.2 vs 5.1 ± 2.0; p = 0.020), whereas diuretic treatment was reduced in cardiac patients. There was no significant difference in serum electrolytes, blood urea, creatinine, nor chloride after the administration of acetazolamide from baseline. Acetazolamide treatment was well tolerated in all patients. Acetazolamide decreases serum HCO3 and PCO2 in PICU cardiac patients with metabolic alkalosis secondary to diuretic therapy. Cardiac postoperative patients present a significant increase in urine output after acetazolamide treatment.

Screening of intraocular pressure before routine pupil dilation for retinal photography: Clinical case report

Introduction Pharmacologic dilation of the pupil results in twice the sensitivity of detection of diabetic retinopathy compared with undilated retinal examination. The potential risk of acute angle-closure glaucoma after pupil dilation has been hypothesized to be higher in Asian patients with diabetes mellitus. Clinical case A 61-year-old man with diabetes mellitus and hypertension was incidentally found to have elevated intraocular pressure (IOP) before routine retinal photography. He was asymptomatic and the visual acuity was 0.67 for both eyes. An ophthalmologist later found he had anatomical narrow-angle borderline glaucoma. Topical administration of pilocarpine and oral administration of acetazolamide were initiated, and laser iridotomy was later performed. IOP screening Among 1736 diabetic and/or hypertensive patients who underwent IOP screening, 31 patients (1.8%) had IOP of any eye persistently higher than 21 mm Hg on at least two occasions. The mean (standard deviation) IOP of the right eye was 24.1 (2.1) mm Hg, while that of the left eye was 24.6 (2.5) mm Hg. Four patients (12.9%) were found to have glaucoma, and treatment was initiated by an ophthalmologist. Therefore further study should be conducted to evaluate the cost-effectiveness of IOP screening among this group of patients.

Comment on the case report "Possible association between acetazolamide administration during pregnancy and multiple congenital malformations".

Comment on the case report "Possible association between acetazolamide administration during pregnancy and multiple congenital malformations".

Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease

To assess the effect of unilateral large vessel disease upon the cerebral hemodynamic autoregulatory status in the basal ganglia of patients with steno-occlusive internal carotid artery (ICA) disease. Twenty-five healthy volunteers and 38 patients with a unilateral symptomatic steno-occlusive ICA lesion and were investigated; 20 with a stenosis >50% and 18 with an occlusion. Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were assessed with pseudo-continuous arterial spin labeling (ASL) magnetic resonance (MR) imaging before and after administration of acetazolamide. When compared to controls, the CVR in patients with ICA stenosis was significantly lower in the middle cerebral artery (MCA) territory (P<0.05), and in the caudate (P<0.05) and lentiform nucleus (P<0.05) of the hemisphere ipsilateral to the stenosis. The CVR in the caudate nucleus contralateral to the stenosis was significantly lower (P<0.05) as well. In patients with ICA occlusion, the CVR in the hemisphere ipsilateral to the occlusion as well as in the contralateral hemisphere was significantly lower in the MCA territory (P<0.05), the caudate (P<0.05) and lentiform nucleus (P<0.05), and in the thalamus (P<0.05). Perfusion ASL MR imaging shows impaired cerebral hemodynamic autoregulation of the basal ganglia in patients with steno-occlusive ICA disease both in the hemisphere ipsilateral as well as in the hemisphere contralateral to the stenosis or occlusion.

The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level-Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation.

Measuring cerebrovascular reactivity with the use of vasodilatory stimuli, such as acetazolamide, is useful for chronic cerebrovascular steno-occlusive disease. The purpose of this study was to evaluate the effects of acetazolamide on the assessment of hemodynamic impairment and functional connectivity by using noninvasive resting-state blood oxygen level-dependent MR imaging. A 20-minute resting-state blood oxygen level-dependent MR imaging scan was acquired with infusion of acetazolamide starting at 5 minutes after scan initiation. A recently developed temporal-shift analysis technique was applied on blood oxygen level-dependent MR imaging data before and after acetazolamide infusion to identify regions with hemodynamic impairment, and the results were compared by using contrast agent-based DSC perfusion imaging as the reference standard. Functional connectivity was compared with and without correction on the signal by using information from temporal-shift analysis, before and after acetazolamide infusion. Visually, temporal-shift analysis of blood oxygen level-dependent MR imaging data identified regions with compromised hemodynamics as defined by DSC, though performance deteriorated in patients with bilateral disease. The Dice similarity coefficient between temporal-shift and DSC maps was higher before (0.487 ± 0.150 by using the superior sagittal sinus signal as a reference for temporal-shift analysis) compared with after acetazolamide administration (0.384 ± 0.107) (P = .006, repeated-measures ANOVA). Functional connectivity analysis with temporal-shift correction identified brain network nodes that were otherwise missed. The accuracy of functional connectivity assessment decreased after acetazolamide administration (P = .015 for default mode network, repeated-measures ANOVA). Temporal-shift analysis of blood oxygen level-dependent MR imaging can identify brain regions with hemodynamic compromise in relation to DSC among patients with chronic cerebrovascular disease. The use of acetazolamide reduces the accuracy of temporal-shift analysis and network connectivity evaluation.

Assessment of cerebral blood perfusion reserve with acetazolamide using 3D spiral ASL MRI: Preliminary experience in pediatric patients

PurposeTo demonstrate the clinical feasibility of a new non-Cartesian cylindrically-distributed spiral 3D pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI) pulse sequence in pediatric patients in quantifying cerebral blood flow (CBF) response to an acetazolamide (ACZ) vasodilator challenge. Materials and methodsMRI exams were performed on two 3 Tesla Philips Ingenia systems using 32 channel head coil arrays. After local institutional review board approval, the 3D spiral-based pCASL technique was added to a standard brain MRI exam and evaluated in 13 pediatric patients (average age: 11.7±6.4years, range: 1.4–22.2years). All patients were administered ACZ for clinically indicated reasons. Quantitative whole-brain CBF measurements were computed pre- and post-ACZ to assess cerebrovascular reserve. Results3D spiral pCASL data were successfully reconstructed in all 13 cases. In 11 patients, CBF increased 2.8% to 93.2% after administration of ACZ. In the two remaining patients, CBF decreased by 2.4 to 6.0% after ACZ. The group average change in CBF due to ACZ was approximately 25.0% and individual changes were statistically significant (p<0.01) in all patients using a paired t-test analysis. CBF perfusion data were diagnostically useful in supporting conventional MR angiography and clinical findings. Conclusion3D cylindrically-distributed spiral pCASL MRI provides a robust approach to assess cerebral blood flow and reserve in pediatric patients.

Novel Polymeric Nanoparticles Intended for Ophthalmic Administration of Acetazolamide

Glaucoma is characterized by increased intraocular pressure (IOP) that results in blindness if it remains untreated. Acetazolamide (AZM) is a carbonic anhydrase inhibitor, mainly used to reduce IOP in the treatment of glaucoma. However, the potential of topical treatment is limited, due to its low permeability across the ocular epithelium. An alternative to overcome this limitation is the incorporation of AZM in nanoparticulate systems, such as polymeric nanocapsules (NCs). In this way, the aim of this work was to prepare and characterize NC formulations containing AZM, using ethylcellulose (EC) and Eudragit® RS100 (EUD) as encapsulating polymers. The formulations showed high encapsulation efficiency. Particle size measurements showed that NCs are in the nanometric range. Comparing both groups of formulations, the NCEC proved to be smaller than those prepared with EUD. The formulations prepared with EC showed negative zeta potentials, while NCs of EUD were positively charged. For both groups of formulations, no more than 30% of drug was released in 120 min. Ex vivo and in vivo studies evidenced that the NCEC formulations were the most efficient, because an increased amount of permeated drug was observed, along with a greater IOP decrease and longer duration of the effect in normotensive rabbits.

Prolonged Mean Transit Time Detected by Dynamic Susceptibility Contrast Magnetic Resonance Imaging Predicts Cerebrovascular Reserve Impairment in Patients with Moyamoya Disease

Background: Evaluating cerebrovascular reserve (CVR) is important for patients with moyamoya disease (MMD). ¹²³I-iodoamphetamine single-photon emission CT (SPECT) with acetazolamide (ACZ) challenge is widely carried out, but using ACZ becomes problematic owing to its off-label use and its adverse effects. Here, we report the efficacy of dynamic susceptibility contrast MRI (DSC-MRI) for the evaluation of CVR in MMD patients. Methods: All 33 MMD patients underwent both SPECT and DSC-MRI at an interval of <10 days from each other (mean age 38.3 years). The region of interest (ROI) was the anterior cerebral artery (ACA) territory, middle cerebral artery (MCA) territory, basal ganglia and cerebellum hemisphere for cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) images. The ratios of the ROIs to the ipsilateral cerebellum were calculated for each parameter and evaluated. The CVR was calculated using images acquired by SPECT before and after ACZ administration. The ratios of DSC-MRI parameters and CVR were compared and evaluated for each ROI. Results: The MTT of the ACA and MCA territories significantly correlated with CVR (p < 0.0001). However, CBF and CBV had no correlation with CVR. The MTT ratio had a threshold of 1.966, with a sensitivity of 68.4% and a specificity of 91.5% for predicting decreased CVR (<10%). Conclusion: MTT had a negative correlation with CVR. DSC-MRI is easy, safe and useful for detecting decreased CVR and can be used as a standard examination in MMD patient's care.

Loss of inhibitory tone on spinal cord dorsal horn spontaneously and nonspontaneously active neurons in a mouse model of neuropathic pain.

Plasticity of inhibitory transmission in the spinal dorsal horn (SDH) is believed to be a key mechanism responsible for pain hypersensitivity in neuropathic pain syndromes. We evaluated this plasticity by recording responses to mechanical stimuli in silent neurons (nonspontaneously active [NSA]) and neurons showing ongoing activity (spontaneously active [SA]) in the SDH of control and nerve-injured mice (cuff model). The SA and NSA neurons represented 59% and 41% of recorded neurons, respectively, and were predominantly wide dynamic range (WDR) in naive mice. Nerve-injured mice displayed a marked decrease in the mechanical threshold of the injured paw. After nerve injury, the proportion of SA neurons was increased to 78%, which suggests that some NSA neurons became SA. In addition, the response to touch (but not pinch) was dramatically increased in SA neurons, and high-threshold (nociceptive specific) neurons were no longer observed. Pharmacological blockade of spinal inhibition with a mixture of GABAA and glycine receptor antagonists significantly increased responses to innocuous mechanical stimuli in SA and NSA neurons from sham animals, but had no effect in sciatic nerve-injured animals, revealing a dramatic loss of spinal inhibitory tone in this situation. Moreover, in nerve-injured mice, local spinal administration of acetazolamide, a carbonic anhydrase inhibitor, restored responses to touch similar to those observed in naive or sham mice. These results suggest that a shift in the reversal potential for anions is an important component of the abnormal mechanical responses and of the loss of inhibitory tone recorded in a model of nerve injury-induced neuropathic pain.

Randomized clinical trial of acetazolamide administration and/or prone positioning in mitigating wound complications following untethering surgeries.

OBJECTIVE No evidence-based guideline has been approved for the postoperative management of pediatric patients with tethered cord syndrome (TCS). The purpose of this randomized clinical trial was to evaluate the effectiveness of prone positioning and acetazolamide administration on complication rates following spinal cord untethering surgeries. METHODS From October 2012 to February 2015, patients with a primary diagnosis of TCS who were admitted to the Children's Medical Center Hospital of Iran were randomly allocated to 1 of 4 intervention modality groups postoperatively: 1) Group A, acetazolamide administration for 10 days; 2) Group B, prone positioning for 10 days; 3) Group C, acetazolamide administration and prone positioning for 10 days; and 4) Group D, no intervention. CSF leakage, CSF collection, wound dehiscence, operative site infection, and secondary surgical wound repair were considered failure. RESULTS A total of 161 patients were enrolled in this study (Group A, n = 39 [24.2%]; Group B, n = 41 [25.5%]; Group C, n = 39 [24.2%]; and Group D, n = 42 [26.1%]). The overall failure rate was 12.42% (20 patients). Complication rates through pooled analyses were as follows: CSF leakage (n = 9, 5.6%), CSF collection (n = 12, 7.5%), wound dehiscence (n = 2, 1.2%), and infection of operation site (n = 3, 1.9%). Two patients (1.2%) required surgical secondary wound repair due to complications. CSF leakage and collection rates were significantly lower in patients who underwent prone positioning (p = 0.042 and 0.036, respectively). The administration of acetazolamide, either isolated or in combination with prone positioning, not only could not significantly lower the complication rates, but also added the burden of side effects. CONCLUSIONS The current study demonstrates the possible role of prone positioning in mitigating the complication rates subsequent to untethering surgeries. Clinical trial registration no.: NCT01867268 ( clinicaltrials.gov ).

Premedication With Single Dose of Acetazolamide for the Control of Referral Shoulder Pain After Laparoscopic Cholecystectomy

Background:The use of laparoscopic surgeries is escalating thanks to their advantages over the open surgeries. However, several complications can be observed following laparoscopy operation. Postoperative pain is a major concern in cholecystectomy surgeries. Pain can be both experienced in operated areas and radiated to the right shoulder. Acetazolamide is used for glaucoma, acute mountain sickness prophylaxis, and epilepsy in few patients with recurrent epilepsy. It seems that patients’ pain can be reduced by preventing carbonic acid production in abdomen after operation.Objectives:We aimed at evaluating if administration of acetazolamide preoperatively could affect early or late postoperative pain following laparoscopic surgery.Patients and Methods:In a randomized-controlled clinical trial study, 70 subjects (30 - 60 years) scheduled for laparoscopic cholecystectomy were included after obtaining a written informed consent. Patients were divided into two groups randomly (intervention and control). The intervention group received 5 mg/kg oral acetazolamide one hour before the operation. The control group did not receive any further medication.Results:Administration of a single dose of acetazolamide did not have any statistically significant impact on sleep quality (P = 1.000). Moreover, there was no statistically significant difference between groups regarding nausea and vomiting on single dose administration of acetazolamide (P = 1.000). Single dose of acetazolamide was associated with statistically significant decrease in shoulder pain immediately after laparoscopy (P = 0.017). However, there was no statistically significant difference regarding shoulder pain between the studied groups 2, 4, 6, 8, 10, 12, and 24 hours after laparoscopy. Single dose of acetazolamide did not significantly affect analgesic administration in 2, 4, 6, 8, 10, 12, and 24 hours after laparoscopy.Conclusions:Single dose of acetazolamide was associated with statistically significant decrease in shoulder pain immediately after laparoscopy. However, this effect was limited to the first postoperative hours and it failed to reduce postoperative pain of right shoulder during 24 hours after the operation.

Acetazolamide reduces postoperative pain following laparoscopic inguinal herniorrhaphy.

Carbonic acid accumulation, which results from CO2 insufflation, can produce visceral and referred pain in the postoperative setting. Acetazolamide inhibits carbonic anhydrase, an enzyme that accelerates carbonic acid formation. We hypothesized that preoperative administration of acetazolamide would decrease postoperative pain in patients undergoing laparoscopic inguinal herniorrhaphy. A retrospective review was conducted of patients who underwent laparoscopic preperitoneal inguinal herniorrhaphy at the Medical College of Wisconsin between October 2012 and September 2014. Beginning in January 2014, patients began receiving 250mg of acetazolamide preoperatively; patients prior to that time did not. The visual analog scale (range 0-10) was used to assess both preoperative pain and postoperative pain. A total of 66 patients underwent laparoscopic inguinal herniorrhaphy during the study interval. Of these, 22 (33%) patients received acetazolamide preoperatively, and 44 (67%) were included as controls. Overall mean pain scores were lower in the acetazolamide group (1.9±1.45 vs 2.9±1.5, p=0.04). Specifically, patients who received acetazolamide reported lower pain scores immediately after surgery (0.6±1.2 vs 1.9±2.3, p=0.01) and on post-op day one (2.3±0.9 vs 4.0±2.1, p=0.04). Total morphine equivalents administered to manage postoperative pain were significantly less for the acetazolamide group (4.3±4.8mg) when compared to the control group (8.9±8.4mg), p=0.04. Perioperative complications did not differ between the groups (p=0.16). Acetazolamide appears to reduce pain in the immediate postoperative setting. Patients who received acetazolamide had lower pain scores postoperatively and required fewer narcotics for pain management prior to discharge.