Severe acute lactic acidosis and hypoglycemia due to isolate tramadol poisoning

Granauro, Patricia; Comite, Vincenzo Di; Lippi, Giuseppe; Marzi, Umberto; Cervellin, Gianfranco

doi:10.4081/ecj.2016.5659

Cited by 4 publications

(4 citation statements)

References 19 publications

(17 reference statements)

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“…Conflicting results have been reported in several studies. Some studies have reported hypoglycemia in tramadol poisoning [5,8,[27][28][29][30][31][32][33][34][35][36] and others have reported elevated blood glucose levels in these individuals [31,37,38]. Consistent with our results, several studies have shown normal blood glucose levels in people with tramadol poisoning [4,8,31,34,36,39,40].…”

Section: Discussionsupporting

confidence: 91%

Effects of naloxone and diazepam on blood glucose levels in tramadol overdose using generalized estimating equation (GEE) model; (an experimental study)

et al. 2021

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Background Tramadol is a synthetic opioid and poisoning is increasing around the world day by day. Various treatments are applied for tramadol poisoning. Due to the unknown effects of tramadol poisoning and some of its treatments on blood glucose levels, this study was conducted to investigate the overdose of tramadol and its common treatments (naloxone, diazepam), and their combination on blood glucose levels in male rats. Methods This study was conducted in 45 male Wistar rats. The animals were randomly divided into five groups of 9. They received a 75 mg/kg dose of tramadol alone with naloxone, diazepam, and a combination of both of these two drugs. On the last day, animals’ tail vein blood glucose levels (BGL) were measured using a glucometer at different times, including before the tramadol injection (baseline) and 1 hour, 3 hours, and 6 hours after wards. The rats were anesthetized and sacrificed 24 h after the last injection. Blood samples were then taken, and the serum obtained was used to verify the fasting glucose concentration. Data were analyzed using SPSS software at a significance level of 0.05 using a one-way analysis of variance (ANOVA) and a generalized estimating equation (GEE). Results According to the GEE model results, the diazepam-tramadol and naloxone-diazepam-tramadol groups showed blood glucose levels five units higher than the tramadol group (p < 0.05). The diazepam-tramadol group had significantly higher blood glucose levels than the naloxone-tramadol group (p < 0.05). The mean blood glucose levels before the intervention, 3 hours and 6 hours after the injection of tramadol did not differ between the groups, but the blood glucose levels 1 hour after the injection of tramadol in the group of naloxone-tramadol were significantly lower than in the control group (p < 0.05). Blood glucose levels did not differ between the groups 24 h after injection of tramadol. Conclusion The results of the present study showed tramadol overdose does not affect blood glucose levels. The diazepam-tramadol combination and the diazepam-naloxone-tramadol combination caused an increase in blood glucose levels.

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Section: Discussionsupporting

confidence: 91%

Effects of naloxone and diazepam on blood glucose levels in tramadol overdose using generalized estimating equation (GEE) model; (an experimental study)

et al. 2021

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“…Con icting results have been reported in several studies. Some studies have reported hypoglycemia in tramadol poisoning [5,6,[23][24][25][26][27][28][29][30][31][32], and others have reported elevated blood glucose levels in these individuals [6,24,33,34]. Consistent with our results, several studies have shown normal blood glucose levels in people with tramadol poisoning [4, 6, 23-25, 35, 36].…”

Section: Discussionsupporting

confidence: 90%

Effects of Naloxone and Diazepam on Blood Glucose Levels in Tramadol Overdose using Generalized Estimating Equation (GEE) Model; (An Experimental Study)

Nakhaee

Farrokhfall

Miri‐Moghaddam

et al. 2021

Preprint

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Background:Tramadol poisoning is increasing around the world day by day. Tramadol is a synthetic opioid. Also, various treatments are applied for tramadol poisoning. Due to the unknown effects of tramadol poisoning and some of its treatments on blood glucose, this study was conducted to investigate the overdose of tramadol and its common treatments (naloxone, diazepam) and their combination on blood glucose in male rats. Methods: This study was conducted in 45 male Wistar rats. The animals were randomly divided into five groups of 9 rats. They received a 75 mg/kg dose of tramadol alone with naloxone, diazepam, and a combination of these two drugs. On the last day, animals' tail vein blood glucose levels (BGL) were measured using a glucometer at different times, including before the tramadol injection (baseline), one hour, three hours, and six hours after the tramadol injection. The rats were anesthetized and sacrificed 24 hours after the last injection. Blood samples were then taken, and the serum obtained was used to verify the fasting glucose concentration. Data were analyzed using SPSS software at a significance level of 0.05 using a one-way analysis of variance (ANOVA) and a generalized estimating equation (GEE).Results: According to the GEE model results, the diazepam and naloxone-diazepam groups showed blood glucose levels five units higher than the tramadol group (p <0.05). The diazepam group had significantly higher blood glucose levels than the naloxone group (p <0.05). The mean blood glucose levels before the intervention, three hours and six hours after the injection of tramadol did not differ between the groups, but the blood glucose levels one hour after the injection of tramadol in the group of naloxone were significantly lower than in the control group (p <0.05). Blood glucose levels did not differ between the groups 24 hours after injection of tramadol.Conclusion: The results of the present study showed that tramadol overdose does not affect blood glucose levels. Diazepam alone and in combination with naloxone caused an increase in blood glucose levels in the tramadol overdose.

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“…There is significant heterogeneity in the types of literature reporting tramadol-associated hypoglycemia especially with trial design, statistical tests, covariates, and study inclusion and exclusion criteria. 4,6-17 Two case-control studies of diabetic and nondiabetic patients by Golightly et al 13 and Fournier et al 9 support our findings that there is a stronger signal for tramadol-associated hypoglycemia in patients not taking diabetes medications. Golightly et al reported an increased risk of hypoglycemia in tramadol patients who were not diabetic compared with oxycodone patients with hypoglycemia who were not diabetic (RR = 3.12 [95% CI = 1.53-6.51]).…”

Section: Discussionsupporting

confidence: 71%

“…There have been 12 reports published about tramadol-induced hypoglycemia in English between 2009 and 2018 representing the United Kingdom, the United States of America, Australia, India, Saudi Arabia, Qatar, Iran, France, Nigeria, Italy, and Taiwan. [6][7][8][9][10][11][12][13][14][15][16][17] Spontaneous, voluntary reporting systems such as the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database serve as a valuable resource for identifying rare side effects that are less likely to emerge during costly, time-limited clinical trials enrolling homogeneous patient populations of limited size. A limitation of FAERS and similar databases is the lack of reliable exposure information as well as a control group, but this can be partially overcome through the use of disproportionality analysis.…”

Section: Introductionmentioning

confidence: 99%

A Review of the Food and Drug Administration Adverse Event Reporting System for Tramadol-Related Hypoglycemia

Juba

Manen²,

Fellows

2019

Ann Pharmacother

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Background: Background: Hypoglycemia is a rare adverse effect of tramadol that is described in the medical literature and package insert. Objective: Objective: The purpose of this study was to review reports of tramadol and hypoglycemia in the Food and Drug Administration Adverse Event Reporting System (FAERS) database to determine a potential association. Methods: Methods: Disproportionality analysis with Bayesian correction was used to compare tramadol and hypoglycemia with other medications in FAERS. The results were considered significant if the fifth percentile of the Empirical Bayesian geometric mean distribution (EB05) >2. Logistic regression odds ratios was used to determine if age, diabetes medications, and renal insufficiency masked the disproportionality of hypoglycemia, with the fifth percentile of the logistic regression odds ratio (LR05) >2 indicating a potential signal. The Interaction Signal Score (INTSS) was computed to determine the influence of predisposing risk factors on the signal. Results: Results: A total of 605 cases of tramadol-associated hypoglycemia were reported, but our results were not significant (EB05: 1.590). Tramadol-associated hypoglycemia was significant in patients who did not take diabetes medications (EB05: 2.256; LR05: 2.2104). Renal insufficiency was not found to increase the risk of tramadol-associated hypoglycemia (INTSS: 0.865). There was a significant signal for tramadol-associated hypoglycemia in patients aged 0 to 1 year (LR05: 3.0240) and 2 to 4 years (LR05: 2.6853). Conclusion and Conclusion and Relevance: Relevance: Results of our analysis suggest a potential signal between hypoglycemia and tramadol use in patients not taking diabetes medications. Our results do not support a predisposition for tramadolassociated hypoglycemia in patients with renal insufficiency, increasing age, and/or diabetes as noted in the tramadol package insert. Abstract:Background: Hypoglycemia is a rare adverse effect (AE) of the central analgesic tramadol that is described in the medical literature and package insert.Objective: The purpose of this study was to review reports of tramadol and hypoglycemia in the Food and Drug Administration Adverse Event Reporting System (FAERS) database to determine a potential association. Methods: Disproportionality analysis with Bayesian correction was used to compare tramadol and hypoglycemia with other medications in FAERS using Empirica Signal Software. The results were considered significant if the fifth percentile of the Empirical Bayesian geometric mean (EBGM) distribution (EB05) > 2. Logistic regression odd-ratios (LROR) was used to determine if age, diabetes medications, and renal insufficiency masked the disproportionality of hypoglycemia with LR05 > 2 indicating a potential signal. The Interaction Signal Score (INTSS) was computed to determine the influence of predisposing risk factors' on the signal.Results: Six hundred and five cases of tramadol associated hypoglycemia were reported in the FAERS database, but our results were not significan...

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Severe acute lactic acidosis and hypoglycemia due to isolate tramadol poisoning

Abstract: The article describes a case of severe acute lactic acidosis and hypoglycemia after intentional ingestion of tramadol overdose.

Cited by 4 publications

References 19 publications

Effects of naloxone and diazepam on blood glucose levels in tramadol overdose using generalized estimating equation (GEE) model; (an experimental study)

Effects of naloxone and diazepam on blood glucose levels in tramadol overdose using generalized estimating equation (GEE) model; (an experimental study)

Effects of Naloxone and Diazepam on Blood Glucose Levels in Tramadol Overdose using Generalized Estimating Equation (GEE) Model; (An Experimental Study)

A Review of the Food and Drug Administration Adverse Event Reporting System for Tramadol-Related Hypoglycemia

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