Methemoglobinemia due to ingestion of at most three pills of pyridium in a 2-year-old: case report and review

Pyridium (phenazopyridine HCl) is a commonly prescribed medication in the treatment of urinary tract infections and is known to cause methemoglobinemia in excessive doses. We report the case of a 2-year-old child who ingested a maximum of three 200-mg tablets (approximately 50 mg/kg) of pyridium and yet developed cyanosis and methemoglobinemia (29.1%), resulting in methylene blue therapy. We urge physicians to consider a period of observation (4-6 h) or to obtain methemoglobin levels in children who ingest even a small number of pyridium tablets because this can represent a toxic dose in a small child.     

Anesthetic management of a patient with methemoglobinemia

Methemoglobinemia results from the oxidation of the ferrous iron in hemoglobin to the ferric iron state. Methemoglobin is incapable of carrying O2, and high levels may impact on O2 delivery to the tissues. Methemoglobinemia may result from congenital deficiencies of enzymes that normally convert methemoglobin to hemoglobin, alterations in the hemoglobin molecule itself or, most commonly, from the ingestion of medications or toxins that oxidize the ferrous iron of hemoglobin. Several issues must be considered when anesthetizing patients with methemoglobinemia, including the potential for decreased O2 delivery, which may be exacerbated by intraoperative blood loss and anemia, interference with normal intraoperative monitoring devices, and the potential for medications to cause or exacerbate methemoglobinemia. We describe a patient with acquired methemoglobinemia from dapsone therapy who required anesthetic care for shoulder arthroscopy. The patient's drug-induced methemoglobinemia was diagnosed intraoperatively during previous anesthesia on the basis of discrepancy between the O2 saturation noted by pulse oximetry and that obtained from arterial blood gas analysis. Anesthetic care for patients with methemoglobinemia is discussed and a review of methemoglobinemia presented.     

Acute renal failure due to bacterial pyelonephritis.

Five patients who presented with acute renal failure in association with urinary tract infection are reported. Renal function improved rapidly on antibacterial therapy and no alternative cause for acute renal failure could be identified. None had previously been known to have renal disease but three of the five had taken considerable amounts of analgesics. The unusual severity of renal functional impairment resulting from urinary tract infection in these patients is unexplained but may relate to previous analgesic abuse and/or delay in treatment. Since acute non-obstructive pyelonephritis may result in severe reversible renal failure, this diagnosis must be considered in patients presenting with acute uraemia.     

Acute Renal Failure due to Bacterial Pyelonephritis

Five patients who presented with acute renal failure in associationwith urinary tract infection are reported. Renal function improvedrapidly on antibacterial therapy and no alternative cause foracute renal failure could be Identified. None had previouslybeen known to have renal disease but three of the five had takenconsiderable amounts of analgesics. The unusual severity of renal functional impairment resultingfrom urinary tract infection in these patients is unexplainedbut may relate to previous analgesic abuse and/or delay in treatment.Since acute non-obstructive pyelonephritis may result in severereversible renal failure, this diagnosis must be consideredin patients presenting with acute uraemia.     

Results of corrective surgery for alkaline reflux gastritis

Reflux alkaline gastritis and esophagitis have been incriminated as a source of symptoms in achlorhydric patients afer operation for duodenal ulcer. Documentation of such pathologic findings has increased due to widespread use of fiberoptic endoscopy. As reported in the literature, results of remedial operations have ranged from encouraging to excellent, and evaluations have been uniformly laudatory. Correlation of the extent of symptoms and of pathologic findings has been difficult, and our results have not been as good as those reported in the literature. During a six-year period, the diagnosis of bile reflux gastritis in 13 patients was based on a characteristic symptom complex, endoscopic appearance, and histopathologic confirmation. Either a Roux-en-Y gastrojejunostomy or a Tanner-Roux 19 was the corrective procedure. There was complete relief of symptoms in five patients (38%) and partial relief in four, but no apparent relief in four others. In at least three of the patients, chronic gastritis and/or esophagitis have persisted and have not improved despite biliary diversion. Tabulation of the results of 13 remedial operations for reflux alkaline gastritis disclosed that copmlete relief of symptoms was achieved in 50% of those who had the Roux-en-Y and in 20% of those who had the Tanner 19 procedure. Based on our findings, we recommend a cautious approach to the surgical management of alkaline gastritis.     

内镜下氩离子凝固术治疗成熟型疣状胃炎35例临床分析

目的探讨内镜下氩离子凝固术(APC)在成熟型疣状胃炎中的治疗价值。方法35例成熟型疣状胃炎患者行APC治疗,氩气流量设定为2L/min,功率40～60W,灼除所有疣状病灶。术后给予奥美拉唑治疗。1个月后随访及胃镜复查。结果35例共146枚成熟型疣状胃炎病灶经APC治疗灼除,治疗次数根据病灶大小决定,平均每枚病灶治疗时间为3.9s(2￣6s)。所有患者未出现出血、穿孔等并发症。随访发现31例患者(88.6%)临床症状消失,内镜显示隆起病灶平伏,黏膜炎症明显改善。4例(11.4%)黏膜炎症改善,但仍有消化道症状。结论内镜下APC治疗成熟型疣状胃炎是一种安全、有效的方法。     

Difference of the clinical course and outcome between dapsone-induced methemoglobinemia and other toxic-agent-induced methemoglobinemia

Context: Acquired methemoglobinemia is a potentially fatal condition that leads to tissue hypoxia. Although the clinical features of methemoglobinemia depend on the methemoglobin levels, the clinical course would differ depending on the causative agents.

Objective: We attempted to clarify this issue by comparing the clinical course of methemoglobinemia caused by dapsone and that caused by other toxic agents.

Materials and methods: A retrospective case–control study was performed. All patients with methemoglobinemia and who were admitted to the emergency department (ED) of our hospital from 1 January 2002 to 31 December 2014 were included.

Results: Of the 34 patients with methemoglobinemia, 15 ingested dapsone (14 with acute overdose and one with chronic therapeutic use) and 19 had been exposed to other toxic agents, such as sodium nitrites, indoxacarb, primaquine, and lidocaine. The clinical characteristics and the course of dapsone-induced and other toxic-agent-induced methemoglobinemia were compared. There was no significant difference in clinical presentation and methemoglobin level (38.5% vs. 35.0%, p?=?0.456) upon their ED arrival between the two groups. However, the methemoglobin level after use of methylene blue and the total dose of methylene blue were higher in patients with dapsone-induced methemoglobinemia than in those with other agent-induced methemoglobinemia (11.9% vs. 1.7%, p?=?0.001, 455?mg vs. 144?mg, p?=?0.006). The majority of dapsone-induced methemoglobinemia (93.3%) required more than 72?h for normalization of the methemoglobin level, despite the use of methylene blue. Five of the study patients died due to multiorgan failure, and all of whom were inpatients with dapsone-induced methemoglobinemia.

Conclusion: The clinical course of dapsone-induced methemoglobinemia was worse than that of other toxic-agent-induced methemoglobinemia despite no significant difference in their initial clinical presentation. Continuous treatment with serial monitoring of the serum methemoglobin is necessary for patients with dapsone-induced methemoglobinemia.     

Chronic methemoglobinemia: Improving hemoglobin saturation monitoring during anesthesia

Methemoglobin interferes with the accuracy of pulse oximetry data. Methemoglobinemia is caused by many factors, both congenital and acquired. However, the increasing usage of dapsone, which converts hemoglobin to methemoglobin, is increasing the number of patients with methemoglobinemia. We present the case of a patient with dapsone-induced methemoglobinemia who was successfully treated with methylene blue, which converts methemoglobin back to hemoglobin. Methemoglobin interferes with the accurate pulse oximetric monitoring of oxyhemoglobin saturation [1—5]. Generally, in the presence of methemoglobin levels greater than 1 g’dL^-1, pulse oximeter readings above 85% underestimate the saturation of functional hemoglobin (the hemoglobin functioning normally with respect to oxygen); readings below 85% overestimate the saturation [2]. These inaccuracies are exaggerated as methemoglobin levels increase or functional hemoglobin saturation decreases [2]. In addition to other causes of methemoglobinemia, the spread of the HIV epidemic and the increasing number of HIV patients receiving dapsone (diaminodiphenylsulfone) as prophylactic treatment forPneumocystis carinii will expand the population of patients with clinical methemoglobinemia who require anesthesia for surgery [6-8]. Virtually all patients treated with dapsone will have levels of methemoglobin sufficient to interfere with pulse oximetric monitoring [7]. We present a case that illustrates these problems and emphasizes the importance of treating methemoglobinemia before the induction of anesthesia to ensure accurate intraoperative monitoring of oxyhemoglobin saturation.     

Fentanyl-contaminated cocaine outbreak with laboratory confirmation in New York City in 2019

BackgroundIllicitly manufactured fentanyl and fentanyl analogues (IMFs) are being increasingly suspected in overdose deaths. However, few prior outbreaks have been reported thus far of patients with laboratory-confirmed IMF toxicity after reporting intent to use only nonopioid substances. Herein we report a case series of nine patients without opioid use disorder who presented to two urban emergency departments (EDs) with opioid toxicity after insufflating a substance they believed to be cocaine.Case reportsOver a period of under three hours, nine patients from five discrete locations were brought to two affiliated urban academic EDs. All patients denied prior illicit opioid use. All patients endorsed insufflating cocaine shortly prior to ED presentation. Soon after exposure, all developed lightheadedness and/or respiratory depression. Seven patients received naloxone en route to the hospital; all had improvement in respiratory function by arrival to the ED. None of the patients required any additional naloxone administration in the ED. All nine patients were discharged home after observation.Blood +/− urine samples were obtained from eight patients. All patients who provided specimens tested positive for cocaine metabolites and had quantifiable IMF concentrations, as well as several detectable fentanyl derivatives, analogues, and synthetic opioid manufacturing intermediates.DiscussionIMF-contamination of illicit drugs remains a public health concern that does not appear to be restricted to heroin. This confirmed outbreak demonstrates that providers should elevate their level of suspicion for concomitant unintentional IMF exposure even in cases of non-opioid drug intoxication. Responsive public health apparatuses must prepare for future IMF-contamination outbreaks.     

Greater curvature antral flattening: A radiologic sign of NSAID-related gastropathy

We have occasionally encountered patients on nonsteroidal antiinflammatory drugs (NSAIDs) in whom double contrast barium studies revealed persistent flattening and stiffening of the distal greater curvature of the stomach. We therefore performed a study to determine the frequency of this finding in patients with NSAID-related gastropathy. Twenty-one cases of erosive gastritis, gastric ulcers, and/or gastric scarring associated with a known history of NSAID use were reviewed by two radiologists who made a joint decision regarding the presence or absence of greater curvature antral flattening. This finding was seen radiographically in five of the 21 patients (24%). Four of the five patients with antral flattening had associated erosions or ulcers in the gastric antrum. The remaining patient had antral flattening as an isolated finding. Our experience suggests that flattening of the greater curvature of the distal antrum, particularly if associated with erosive gastritis or gastric ulcers, is a useful radiologic sign of NSAID-related gastropathy.     

Aphrodisiac Drug‐Induced Hemolysis

Volatile alkyl nitrites have been used during the past decades for “recreational purposes,” and for intensifying sexual experience. Their use has been associated with methemoglobinemia and hemolysis. We report three patients who presented over the past year with acute hemolysis after inhalation of butyl nitrite, two of them had glucose‐6‐phosphate dehydrogenase (G6PD) deficiency.     

Atrophic gastritis as a premalignant condition

Chronic (atrophic) gastritis is a progressive disease which in a small proportion of patients leads to severe (total) atrophy (severe grade of chronic gastritis) of the antral or body mucosa or both. Chronic gastritis is a premalignant condition which favours the development of gastric cancer. Chronic gastritis precedes gastric cancer and shows a severalfold increase in the risk of gastric cancer compared to subjects with histologically normal stomach. Several tentative modifications to the estimate of the risks may be presented: (i) a severe risk of developing gastric cancer is restricted to subjects with a severe grade of chronic gastritis (ii) the risk of gastric cancer is increased in subjects who have either severe antral or body chronic gastritis, the risk being approximately three to five times higher in the antral chronic gastritis (B-type of gastritis) than in the body chronic gastritis (A type of gastritis); (iii) the antral and body chronic gastritis are independent risk factors for gastric cancer, the joint risks being multiplicands of the marginal risks i.e., the estimated risk is highest in those subjects who show severe chronic gastritis in both the antrum and the body (AB type of gastritis); (iiii) the chronic gastritis mediated gastric cancer risk is limited to gastric cancers of the intestinal type, and thus covers only a proportion of all cases of gastric cancer. In the highest risk groups it may be estimated that the probability of a subject developing gastric cancer in subsequent decades is up to 30% if the subject is a young man who has severe chronic gastritis in his antrum, or who has it coexistently in the antrum and body.     

Electrophoretic and functional variants of NADH-methemoglobin reductase in hereditary methemoglobinemia

The electrophoretic mobility and activity of NADH-methemoglobin reductase in erythrocytes of patients with hereditary methemoglobinemia, obligatory heterozygotes, and normal subjects were examined. Six distinct electrophoretic variants were found in studies of erythrocytes from members of ten different families. Five variants (Boston Slow, Duarte, Princeton, Puerto Rico, and California) were associated with significant methemoglobinemia and moderate to marked decreases in enzymic activity. Precise correlations between levels of NADH-methemoglobin reductase activity, electrophoretic mobility, and clinical severity of methemoglobinemia, however, could not be drawn. One variant (Boston Fast) was associated with almost normal activity and very minimal methemoglobinemia. Nine members from three generations of two Italian families were found to have two bands with NADH-methemoglobin reductase activity in their erythrocytes, one with normal mobility and one with a mobility identical with that of Boston Fast. No functional or clinical impairment could be attributed to this abnormality. The observations made in this investigation were consistent with an autosomal recessive mode of inheritance of multiple alleles for NADH-methemoglobin reductase. As has been shown to be true for hemoglobin and glucose-6-phosphate dehydrogenase, multiple aberrations in the NADH-methemoglobin reductase of human erythrocytes apparently exist, some with and some without functional consequences.Two bands with NADPH-methemoglobin reductase activity with electrophoretic mobilities distinct from those of the NADH-methemoglobin reductase were found in human erythrocytes. These bands were normal in hemolysates of erythrocytes from patients with hereditary methemoglobinemia, but were absent from the hemolysate of erythrocytes deficient in NADPH-methemoglobin reductase activity. These latter erythrocytes, however, contained normal concentrations of methemoglobin and had a normal ability to reduce methemoglobin in vitro. These observations were most consistent with the thesis that the NADH-methemoglobin reductase, distinct from any NADPH-methemoglobin reductase, was the major system responsible for the reduction of methemoglobin to hemoglobin in human erythrocytes.     

The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients

It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.     

Treatment of high-risk,refractory acquired methemoglobinemia with automated red blood cell exchange

Ingestion of strong oxidant substances may result in acquired methemoglobinemia, a clinical condition in which the oxidized blood hemoglobin is incapable of delivering oxygen to the tissues, and the patient becomes cyanotic. Traditional first-line therapy consists of infusion of methylene blue, whose action depends on the availability of reduced nicotinamide adenine nucleotide phosphate (NADPH) within the red blood cell (RBC). Some patients, particularly those who are deficient in glucose-6-phosphate dehydrogenase (G6PD), will not benefit from methylene blue. In these patients, and in some patients who have ingested very strong oxidants, methylene blue may also precipitate Heinz body hemolytic anemia. We present a case of severe, acquired methemoglobinemia in a 26-month-old, 9.8-kg boy with G6PD deficiency. He was cyanotic, in respiratory failure, intubated in a pediatric intensive care unit. In typical fashion, he did not respond to methylene blue. Manual exchange of two whole blood volumes, performed over 4 hr, also failed to resolve his severe methemoglobinemia. An automated RBC exchange (1.3 RBC volume), lowered his methemoglobin content from 31.8% to 7% in a single 40-min procedure. Thereafter his methemoglobin level continued to decrease rapidly and spontaneously. He was discharged home 2 days later, with 0.4% methemoglobin. To our knowledge, this is the first report to demonstrate the (potentially superior) effectiveness of automated RBC exchange for treatment of patients with high-risk acquired methemoglobinemia, that is, those with G6PD deficiency or who have ingested strong oxidants. J. Clin. Apheresis 13:28–31, 1998. © 1998 Wiley-Liss, Inc.     

Whole bowel irrigation in dapsone intoxication with persistent methemoglobinemia

Dapsone intoxication can be a life-threatening condition due its enterohepatic recirculation pharmacokinetics, and therefore, persistent methemoglobinemia development. We describe a case of a 17-year-old girl who was admitted 4 h after ingesting 5 g of dapsone. She presented methemoglobinemia (39%) and showed clinical signs of toxicity (cyanosis and altered mental status) despite mechanical ventilation. Multiple activated charcoal dosis and methylene blue infusions were performed. Notwithstanding initial improvement, a pattern of peaks and valleys was observed in serial methemoglobinemia measurements, with cyclic states of hypoxemia. On account of enterohepatic recirculation pharmacokinetics, clearance was enhanced by whole bowel irrigation. After 7 days of hospitalization, she was discharged in good general condition.     

Long-Term Outcome Following Programmed Electrical Stimulation in Patients with High-Grade Ventricular Ectopy

To determine if programmed electrical stimulation (PES) could be utilized to identify patients with high-grade ventricular ectopy at low- or high-risk for sudden cardiac death, we performed PES in 40 patients with high-grade ventricular ectopy refractory to conventional antiarrhythmic agents. Twenty-one patients had a previous myocardial infarction, five had cardiomyopathy, six had hypertension, three had valvular heart disease and five had no known structural heart disease. The mean age was 50 years (range, 18 to 76). During programmed ventricular stimulation, eight patients had inducible sustained (more than 30 seconds) monomorphic ventricular tachycardia (Group I) but in 32 patients sustained ventricular tachycardia was not inducible (Group II). None of the five patients without structural heart disease were inducible while seven out of 21 (33%) patients with previous myocardial infarction had inducible ventricular tachycardia (VT). Antiarrhythmic therapy was instituted in patients with inducible VT; patients without inducible VT did not receive antiarrhythmic agents. In Group I, seven of the eight patients are alive (mean follow-up, 16 months) and in Group II, 28 of the 32 patients are alive (mean follow-up, 17 months). None of the five deaths were sudden. We conclude that in the absence of antiarrhythmic therapy, the incidence of sudden cardiac death is very low in patients with high-grade ventricular ectopy who do not have inducible monomorphic ventricular tachycardia during programmed ventricular stimulation.     

Severe course of delirium tremens. Results of treatment and late prognosis

80 patients (P) (68 men and twelve women) with the diagnosis of delirium tremens were retrospectively analyzed and reexamined over a period of ten years (1974 to 1984). Included were only patients who--after failure of oral medication--required intravenous therapy with Chlomethiazol and thereby intensive care treatment. Mean age was 46.2 (26 to 75) years. During the observation period delirium tremens increased in frequency by 11% each year. Nine patients had two, six patients three and two patients four episodes of delirium tremens. In 86.7% delirium tremens occurred with fatty liver and alcoholic hepatitis, epileptic seizures, cirrhosis and hepatic coma, gastrointestinal hemorrhage and pancreatitis. Eight patients (10%) died in hospital at a mean age of 53.2 years. None of the deceased had less than three (on average four) complicating or associated diseases. These were mostly pneumonia, cirrhosis, hepatic coma, and gastrointestinal hemorrhage. The mean duration of intravenous Chlomethiazol therapy was 4.7 (0.25 to 20) days, the applied dose 26.2 (0.8 to 78.6) grams, there being no significant difference between survivors and non-survivors. Of the 72 survivors 62 were invited for follow-up examination after an average of five years. During this period another twelve patients (15%) died of pneumonia, gastrointestinal bleeding, cardiocirculatory failure and accidents. Life expectancy was only 9.3 years. Of 29 patients who came for follow-up, 55% showed clinical evidence of alcohol dependency, 65% had elevated gamma-glutamyl-transferase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cluster Headache After Head Injury

SYNOPSIS
Four patients developed cluster headaches after minor head injuries that caused no permanent neurologic or CT abnormalities. None had had headaches previously. The headaches of the three whose histories were known in detail either corresponded to the injury site or evolved from an earlier headache that did. Nerve injury is suggested as the mechanism by which trauma could initiate cluster headache.     

Pourquoi et comment surveiller une gastrite chronique?

Stomach cancer remains present in France (6,000 new cases per year).The background is fully known: atrophic gastritis and gastric intestinal metaplasia. This frequent situation, found in 25% of upper tract endoscopies using RUs, is not currently covered by any monitoring recommendations. However, 1.8% of patients showing these histological anomalies develop a gastric adenocarcinoma within the following 10 years. The increased risk factors for atrophic gastritis are also known, mainly severe atrophic gastritis with extension to the stomach as a whole, family antecedents, nicotine dependence, and above all the presence of dysplasia. The results for two large-scale cohorts (in Hong Kong and Europe) strongly suggest that apart from patients showing dysplasia, who obviously have to be monitored, the presence of one of the various increased risk factors associated with atrophic gastritis justifies regular endoscopic and histological monitoring of the persons concerned.