CENTRAL RETINAL VEIN OCCLUSION ASSOCIATED WITH USE OF AMYL NITRITE "POPPERS".

PURPOSE: To report a case of central retinal vein occlusion in a young patient after the use of amyl nitrate "poppers." METHODS: Description of the patient's clinical history, ophthalmic examination, retinal imaging, and treatment. RESULTS: A 38-year-old man presented with a central retinal vein occlusion in his right eye after inhaling amyl nitrite "poppers." There appeared to be a definitive temporal association between poppers use and both the onset of the vein occlusion and the patient's visual scotomata, which recurred immediately after drug use multiple times. Optical coherence tomography displayed cystic macular edema, which was treated with intravitreal bevacizumab. The patient's hypercoagulable laboratory workup was negative. CONCLUSION: This is the first report of a central retinal vein occlusion associated with poppers inhalation. A high index of suspicion for poppers use should be maintained in young patients who present with retinal vein occlusion, particularly in homosexual patients with a normal laboratory workup that fails to reveal a hypercoagulable etiology.

Syncope and Methemoglobinemia Preceded by Amyl Nitrite 'Popper' Inhalation.

INTRODUCTION: Methemoglobinemia represents an uncommon but potentially serious cause of presentation to the emergency department, resulting in hypoxemia and even death. The symptoms and clinical findings in this condition can be nonspecific and therefore methemoglobinemia can be easily missed if the clinician is not familiar with it. This report presents a case caused by recreational drug use which has rarely been documented previously. CASE REPORT: A 23-year-old male with a history of asthma presents to the emergency department for an episode of syncope after inhalation of amyl nitrite "poppers". He had normal vitals other than tachycardia but was found to have nailbed and perioral cyanosis, a classic but uncommon presentation that is demonstrated in the included clinical image. He was found to have methemoglobinemia caused by his use of amyl nitrite and received supportive care but did not require methylene blue. CONCLUSION: Emergency physicians should familiarize themselves with the classic physical exam findings in methemoglobinemia in order to identify and treat this condition promptly. While this patient had a good outcome with only supportive care and observation, his presentation and the etiology of his condition offer an important teaching point. The possibility of methemoglobinemia after recreational "popper" use should be considered when working up a patient who presents with cyanosis and hypoxemia.

Management of cyanide toxicity in patients with burns.

The importance of cyanide toxicity as a component of inhalational injury in patients with burns is increasingly being recognised, and its prompt recognition and management is vital for optimising burns survival. The evidence base for the use of cyanide antidotes is limited by a lack of randomised controlled trials in humans, and in addition consideration must be given to the concomitant pathophysiological processes in patients with burns when interpreting the literature. We present a literature review of the evidence base for cyanide antidotes with interpretation in the context of patients with burns. We conclude that hydroxycobalamin should be utilised as the first-line antidote of choice in patients with burns with inhalational injury where features consistent with cyanide toxicity are present.

Silas Weir Mitchell on epilepsy therapy in the late 19th to early 20th centuries.

Silas Weir Mitchell (1829-1914), one of the fathers of American neurology, is well known for many contributions to neurology. However, his efforts in epilepsy are overshadowed by his other accomplishments. Mitchell introduced a new bromide preparation, lithium bromide, as a viable therapy. His most widely accepted contribution to the field was the introduction of inhaled amyl nitrite for early termination of seizures accompanied by an appropriate aura. Despite the prevalent views on lifestyle modification as a treatment for epilepsy during this time period, as well as Mitchell's own development of the "rest cure" for certain disease states, he was not a proponent of these types of interventions for epilepsy, nor did he support interventions focused on other organ systems, such as abdominal or gynecologic surgery. Mitchell had distinct opinions on the treatment of epilepsy, and helped to advance its therapeutics during his career.

Comparison of the relative propensities of isoamyl nitrite and sodium nitrite to ameliorate acute cyanide poisoning in mice and a novel antidotal effect arising from anesthetics.

Isoamyl nitrite has previously been considered acceptable as an inhaled cyanide antidote; therefore, the antidotal utility of this organic nitrite compared with sodium nitrite was investigated. To facilitate a quantitative comparison, doses of both sodium nitrite and isoamyl nitrite were given intraperitoneally in equimolar amounts to sublethally cyanide-challenged mice. Righting recovery from the knockdown state was clearly compromised in the isoamyl nitrite-treated animals, the effect being attributable to the toxicity of the isoamyl alchol produced during hydrolysis of the isoamyl nitrite to release nitrite anion. Subsequently, inhaled aqueous sodium nitrite aerosol was demonstrated to ameliorate sublethal cyanide toxicity, when provided to mice after the toxic dose, by the more rapid recovery of righting ability compared to that of the control animals given only the toxicant. Aerosolized sodium nitrite has thus been shown by these experiments to have promise as a better alternative to organic nitrites for development as an inhaled cyanide antidote. The inhaled sodium nitrite led to the production of NO in the bloodstream as determined by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. The aerosol delivery was performed in an unmetered inhalation chamber, and in this study, no attempt was made to optimize the procedure. It is argued that administration of an effective inhaled aqueous sodium nitrite dose in humans is possible, though just beyond the capability of current individual metered-dose inhaler designs, such as those used for asthma. Finally, working at slightly greater than LD50 NaCN doses, it was fortuitously discovered that (i) anesthesia leads to significantly prolonged survival compared to that of unanesthetized animals and that (ii) the antidotal activity of nitrite anion was completely abolished under anesthesia. Plausible explanations for these effects in mice and their practical consequences in relation to testing putative cyanide antidotes are discussed.

Does amyl nitrite have a role in the management of pre-hospital mass casualty cyanide poisoning?

CONTEXT: Amyl nitrite has been recommended as a cyanide antidote for several decades. Its antidotal properties were initially attributed to induction of methemoglobin and later to a nitric oxide mediated hemodynamic effect. The ease of administration and alleged rapid clinical effect would recommend its wide use in the pre-hospital management of mass casualty cyanide poisoning; yet there are concerns regarding the use of amyl nitrite for this indication. OBJECTIVE: Review the data on amyl nitrite in cyanide poisoning and evaluate its efficacy and safety in mass casualty cyanide poisoning. METHODS: A literature search utilizing PubMed, Toxnet, textbooks in toxicology and pharmacology, and the bibliographies of the articles retrieved identified 17 experimental studies and human reports on the use of amyl nitrite in cyanide poisoning, and 40 additional articles on amyl nitrite's properties and adverse effects. One paper was excluded as it was a conference abstract with limited data. MECHANISMS OF ACTION: The antidotal properties of amyl nitrite were attributed initially to induction of methemoglobinemia and later to nitric oxide mediated vasodilation. EXPERIMENTAL STUDIES: Animal studies on the use of amyl nitrite in cyanide poisoning are limited, and their results are inconsistent, which makes their extrapolation to humans questionable. HUMAN STUDIES: Clinical reports are limited in number and the part played by amyl nitrite relative to the other treatments administered (e.g. life support, sodium nitrite, and sodium thiosulfate) is unclear. ADVERSE EFFECTS: Amyl nitrite can be associated with potentially serious adverse reactions such as hypotension, syncope, excessive methemoglobinemia, and hemolysis in G6PD deficient patients. These effects are more pronounced in young children, in the elderly, and in patients with cardiac and pulmonary disorders. Dose regimen. The method of administration of amyl nitrite (breaking pearls into gauze or a handkerchief and applying it intermittently to the victim's nose and mouth for a few minutes) is not easily controlled, might result in under- or over-dosing, can prevent the caregiver from administering life support, and possibly expose him/her to amyl nitrite's adverse effects. CONCLUSIONS: Administration of amyl nitrite in mass casualty cyanide poisoning can result in unnecessary morbidity and may interfere with the proper management of the incident and the required supportive treatment and rapid evacuation. In the authors' opinion these drawbacks make the use of amyl nitrite in pre-hospital mass casualty cyanide poisoning unwarranted.

Nitrates and nitrites in the treatment of ischemic cardiac disease.

The organic nitrite, amyl of nitrite, was initially used as a therapeutic agent in the treatment of angina pectoris, but was replaced over a decade later by the organic nitrate, nitroglycerin (NTG), due to the ease of administration and longer duration of action. The administration of organic nitrate esters, such as NTG, continues to be used in the treatment of angina pectoris and heart failure since the birth of modern pharmacology. Their clinical effectiveness is due to vasodilator activity in large veins and arteries through an as yet unidentified method of delivering nitric oxide (NO), or a NO-like compound. The major drawback is the development of tolerance with NTG, and the duration and route of administration with amyl of nitrite. Although the nitrites are no longer used in the treatment of hypertension or ischemic heart disease, the nitrite anion has recently been discovered to possess novel pharmacologic actions, such as modulating hypoxic vasodilation, and providing cytoprotection in ischemia-reperfusion injury. Although the actions of these 2 similar chemical classes (nitrites and organic nitrates) have often been considered to be alike, we still do not understand their mechanism of action. Finally, the nitrite anion, either from sodium nitrite or an intermediate NTG form, may act as a storage form for NO and provide support for investigating the use of these agents in the treatment of ischemic cardiovascular states. We review what is presently known about the use of nitrates and nitrites including the historical, current, and potential uses of these agents, and their mechanisms of action.

Inhaled amyl nitrite effectively reverses acute catastrophic thromboxane-mediated pulmonary hypertension in pigs.

Acute catastrophic pulmonary vasoconstriction frequently leads to cardiovascular collapse. Rapid and selective pulmonary vasodilation is desired in order to restore haemodynamic stability. This pilot study examined the effectiveness of inhaled amyl nitrite as a selective pulmonary vasodilator. Nine adult swine were anaesthetized. Acute pulmonary hypertension with haemodynamic collapse was induced with a bolus administration of a thromboxane analogue, U46619. Six animals then received a capsule of amyl nitrite. The administration of inhaled amyl nitrite decreased mean pulmonary artery pressure from 42 +/- 3 to 22 +/ 3 mmHg at five minutes (p < 0.05), with a concomitant increase in cardiac output and mean arterial pressure. Pulmonary vascular resistance decreased from 4889 +/- 1338 to 380 +/- 195 dyne. sec. cm(-5) (by 92% from the maximal pulmonary hypertension change), with significant improvement in systemic haemodynamics. During acute thromboxane-mediated pulmonary hypertension with cardiovascular collapse, prompt administration of inhaled amyl nitrite was effective in restoring pulmonary and systemic haemodynamics within five minutes.

Hydroxocobalamin: improved public health readiness for cyanide disasters.

The United States is under the constant threat of a mass casualty cyanide disaster from industrial accidents, hazardous material transportation incidents, and deliberate terrorist attacks. The current readiness for cyanide disaster by the emergency medical system in the United States is abysmal. We, as a nation, are simply not prepared for a significant cyanide-related event. The standard of care for cyanide intoxication is the cyanide antidote kit, which is based on the use of nitrites to induce methemoglobinemia. This kit is both expensive and ill suited for out-of-hospital use. It also has its own inherent toxicity that prevents rapid administration. Furthermore, our hospitals frequently fail to stock this life-saving antidote or decline to stock more than one. Hydroxocobalamin is well recognized as an efficacious, safe, and easily administered cyanide antidote. Because of its extremely low adverse effect profile, it is ideal for out-of-hospital use in suspected cyanide intoxication. To effectively prepare for a cyanide disaster, the United States must investigate, adopt, manufacture, and stockpile hydroxocobalamin to prevent needless morbidity and mortality.

The role of nitric oxide synthase/nitric oxide in vascular smooth muscle control.

Vascular compliance is dependent on endogenous and exogenous sources of nitric oxide (NO). In a discussion of therapeutics and NO derived via nitric oxide synthase (NOS) enzymes, it is necessary to examine the pathways of each drug to provide the clinical perfusionist with a greater understanding of the role of NOS/NO in vascular function. Endothelial-derived NO is a contributor in the vasoregulation of vascular smooth muscle. Therapeutics seek to mimic the vasodilatory effects of the endogenous NO. The therapeutics included in this review are nitroglycerin, nitroprusside, amyl nitrite, and inhalation of NO. L-Arginine supplementation provides additional substrate for the endogenous pathway that can augment NO production. NO is a small bioactive molecule involved in various biochemical pathways. Dysregulation of NO production can impair normal physiologic control of vascular compliance. Therefore, the purpose of this review is to provide the perfusionist with an understanding of the biochemical and pharmacological aspects of NOS/NO associated with vascular function.

Treatment of cyanide poisoning in an industrial setting.

Thirty-seven employees were exposed to cyanide between 1956 and 1985. One was found dead. Thirty-six employees were treated; most were given nitrite and oxygen. Some received oxygen alone. All recovered completely. One-third of these employees were unconscious. One was convulsing. Most were discharged home at 6 h post-exposure. Some employees remained at the plant to work an additional shift. Amyl nitrite and/or oxygen were the only agents used with 33 employees. Forced oxygen was administered to the unconscious, apneic employees. Three employees were given sodium nitrite and sodium thiosulfate iv. Treatment generally began within 3 min. In 5 to 20 min all of the unconscious employees reacted positively to the use of forced oxygen and forced amyl nitrite or sodium nitrite. There were no residual effects except headache and transient loss of appetite. Amyl nitrite and oxygen have been effective tools in the treatment of cyanide intoxication at this plant site. There have been no intercurrent or residual drug effects that outweigh the life-saving capacity of these agents. Sodium nitrite should be employed if the use of oxygen and amyl nitrite fail to improve the cardiovascular status/level of consciousness in 5-10 min.

The clinical experience of acute cyanide poisoning.

The authors reviewed the clinical manifestations, complications, and the prognosis affected by Lilly Cyanide Antidote in 21 victims of acute cyanide poisoning over a 10-year period. The clinical signs and symptoms in cyanide poisoning are variable. Among 21 cases, loss of consciousness (15), metabolic acidosis (14), and cardiopulmonary failure (9) were the three leading manifestations of cyanide intoxication. Anoxic encephalopathy (6) was not uncommon in the severely intoxicated victims. Diabetes insipidus (1) or clinical signs and symptoms mimicking diabetes insipidus (3) may be an ominous sign to encephalopathy victims. The major cause of fatal cyanide poisoning is the intentional ingestion of cyanide compounds as part of a suicide attempt. Decrease of arteriovenous difference of O2 partial pressure may be a clue for the suspicion of cyanide intoxication. Although the authors cannot show a statistically significant difference (P = .47) for the Lilly cyanide antidote kit in terms of improving the survival rate for victims of cyanide poisoning, the antidote kit was always mandatory in our study in the cases of severely intoxicated victims who survived. Early diagnosis, prompt, intensive therapy with antidote, and supportive care are still the golden rules for the treatment of acute cyanide poisoning, whether in the ED or on the scene.

[From Thomas Lauder-Brunton to endogenous nitrates]. / Von Thomas Lauder-Brunton zu den endogenen Nitraten.

While nitrates have been in clinical use for more than 100 years, their mode of action is of rather recent discovery. Nitrates act by the release of the free radical NO (nitric oxide) which stimulates the cyclic guanosine monophosphate as vasodilatator and as inhibitor of platelet function. The endogenous nitrate NO is derived from L-arginine catalyzed by nitric oxide synthase, a recently cloned enzyme. Nitrates and other nitro-vasodilatators act similarly to the endogenous nitrate, whereby a basal release of NO in the vascular wall reduces the effect of nitro-vasodilatators. Therefore, drugs are particularly effective in endothelium-free vessel segments and in veins, where the basal release of NO is low. A recently discovered effect of nitro-vasodilatators is the inhibition of thrombin and angiotensin II-induced production of endothelin. Insofar the L-arginine/NO metabolism acts as an important regulator in the vessel wall and has a protective role in the circulation by its antispastic and antithrombotic principle.

Subtle features of the hemodynamic response to amyl nitrite inhalation: new aspects of an old tool.

Although amyl nitrite inhalation (ANI) antedates all current short acting vasodilators as a clinically useful pharmacologic stressor, few clinicians are aware of the subtle hemodynamic actions of this agent. This study examined transients in left and right heart hemodynamics after ANI in seven men (ages 44 +/- 7 years) undergoing elective cardiac catheterization. High-fidelity central aortic (AoP), left ventricular (LVP), pulmonary artery (PAP), right ventricular (RVP), and right atrial (RAP) pressures were simultaneously recorded from left and right heart multisensor catheters. As expected, ANI caused an acute fall in Ao pressure (27%; p < 0.01) and reflex tachycardia (p < 0.001). Little change was noted in PAP, RVP, RAP, or LV end-diastolic pressures or the time constant of LV isovolumetric relaxation (tau). LV ejection time decreased 23 +/- 10 ms (p < 0.05) and RV ejection time did not change. Baroreflex sensitivity was similar during pressure fall and recovery (6.4 +/- 4.5 vs. 6.1 +/- 3.6 ms/mmHg), however hysteresis (p < 0.05) was noted. Aortic pressure waveforms also changed following ANI. Changes were determined to be in part a consequence of the attenuation and delay in arterial wave reflections. This study extends the understanding of the complex nature of the hemodynamic response associated with ANI.

Amyl nitrite: use as a smooth muscle relaxant in difficult preterm cesarean section.

Amyl nitrite is a smooth muscle relaxant that has been used clinically to facilitate uterine relaxation in difficult deliveries. In this retrospective study, we evaluate the safety of amyl nitrite use during preterm cesarean deliveries, and we assess possible advantageous effects on surgical incision choice. Women who received amyl nitrite cesarean section were compared to a control group matched for gestational age, fetal presentation, and mode of delivery who did not receive amyl nitrite. There were no statistical differences between the groups in the independent variables (maternal age, parity, medical or obstetric history, type of anesthesia, anesthesia or obstetric attending physician, antepartum hematocrit, or neonatal weight). Outcome (dependent) variables (estimated blood loss, Apgar scores, postpartum hematocrit, cord gases, or postpartum complications) were assessed, and there were no significant differences between the groups. Low transverse cesarean section was performed more frequently in the amyl nitrite group (58 of 64) than in the comparison group (48 of 64) (p less than 0.03). Considering the 128 women with and without amyl nitrite together, the decrease in hematocrit observed postpartum was greater after classic section (7%) than after low transverse section (4%) (p less than 0.002). We conclude that the use of amyl nitrite during preterm cesarean section poses no threat to mother or fetus and may facilitate delivery by allowing the performance of a low transverse rather than a classic cesarean section without maternal or neonatal complications.