The Impact of Inflammation on Thermal Hyperpnea: Relevance for Heat Stress and Febrile Seizures.

Extreme heat caused by climate change is increasing the transmission of infectious diseases, resulting in a sharp rise in heat-related illness and mortality. Understanding the mechanistic link between heat, inflammation, and disease is thus important for public health. Thermal hyperpnea, and consequent respiratory alkalosis, is crucial in febrile seizures and convulsions induced by heat stress in humans. Here, we address what causes thermal hyperpnea in neonates and how it is affected by inflammation. Transient receptor potential cation channel subfamily V member 1 (TRPV1), a heat-activated channel, is sensitized by inflammation and modulates breathing and thus may play a key role. To investigate whether inflammatory sensitization of TRPV1 modifies neonatal ventilatory responses to heat stress, leading to respiratory alkalosis and an increased susceptibility to hyperthermic seizures, we treated neonatal rats with bacterial LPS, and breathing, arterial pH, in vitro vagus nerve activity, and seizure susceptibility were assessed during heat stress in the presence or absence of a TRPV1 antagonist (AMG-9810) or shRNA-mediated TRPV1 suppression. LPS-induced inflammatory preconditioning lowered the threshold temperature and latency of hyperthermic seizures. This was accompanied by increased tidal volume, minute ventilation, expired CO2, and arterial pH (alkalosis). LPS exposure also elevated vagal spiking and intracellular calcium concentrations in response to hyperthermia. TRPV1 inhibition with AMG-9810 or shRNA reduced the LPS-induced susceptibility to hyperthermic seizures and altered the breathing pattern to fast shallow breaths (tachypnea), making each breath less efficient and restoring arterial pH. These results indicate that inflammation exacerbates thermal hyperpnea-induced respiratory alkalosis associated with increased susceptibility to hyperthermic seizures, primarily mediated by TRPV1 localized to vagus neurons.

Postoperative exacerbated cough hypersensitivity syndrome induces dramatic respiratory alkalosis, lactatemia, and electrolyte imbalance.

BACKGROUND: The perioperative management of patients with chronic cough or cough hypersensitivity syndrome and its sometimes severe effects is currently under-researched and under-reported. CASE PRESENTATION: A 46-year-old female patient with a history of chronic cough and Cough Hypersensitivity Syndrome. After laparoscopic hiatoplasty and anterior fundoplication under general anesthesia, experienced a pronounced exacerbation of coughing symptoms. Despite prompt and extensive treatment involving antitussives, inhalants, anxiolytics, and sedatives, the symptoms remained uncontrollable. Within a few hours, the patient developed a respiratory alkalosis with severe and life-threatening electrolyte shift (pH 7.705, pCO2 1.72 kPa, K+ 2.1 mmol/l). Lactatemia lasted for more than 12 hours with values up to 6.6 mmol/l. Acute bleeding, pneumothorax, and an acute cardiac event were ruled out. Deep analgosedation and inhalation of high-percentage local anesthetics were necessary to manage the clinical symptoms. CONCLUSIONS: This case highlights the challenging nature of chronic cough and hypersensitivity syndrome perioperatively. A tailored anesthesiologic approach, exclusion of other provoking medical problems, and knowledge of possible management and treatment options are key.

Cerebral uptake of microvesicles occurs in normocapnic but not hypocapnic passive hyperthermia in young healthy male adults.

Passive hyperthermia causes cerebral hypoperfusion primarily from heat-induced respiratory alkalosis. However, despite the cerebral hypoperfusion, it is possible that the mild alkalosis might help to attenuate cerebral inflammation. In this study, the cerebral exchange of extracellular vesicles (microvesicles), which are known to elicit pro-inflammatory responses when released in conditions of stress, were examined in hyperthermia with and without respiratory alkalosis. Ten healthy male adults were heated passively, using a warm water-perfused suit, up to core temperature + 2°C. Blood samples were taken from the radial artery and internal jugular bulb. Microvesicle concentrations were determined in platelet-poor plasma via cells expressing CD62E (activated endothelial cells), CD31+ /CD42b- (apoptotic endothelial cells), CD14 (monocytes) and CD45 (pan-leucocytes). Cerebral blood flow was measured via duplex ultrasound of the internal carotid and vertebral arteries to determine cerebral exchange kinetics. From baseline to poikilocapnic (alkalotic) hyperthermia, there was no change in microvesicle concentration from any cell origin measured (P-values all >0.05). However, when blood CO2 tension was normalized to baseline levels in hyperthermia, there was a marked increase in cerebral uptake of microvesicles expressing CD62E (P = 0.028), CD31+ /CD42b- (P = 0.003) and CD14 (P = 0.031) compared with baseline, corresponding to large increases in arterial but not jugular venous concentrations. In a subset of seven participants who underwent hypercapnia and hypocapnia in the absence of heating, there was no change in microvesicle concentrations or cerebral exchange, suggesting that hyperthermia potentiated the CO2 /pH-mediated cerebral uptake of microvesicles. These data provide insight into a potential beneficial role of respiratory alkalosis in heat stress. KEY POINTS: The hyperthermia-induced hyperventilatory response is observed in most humans, despite causing potentially harmful reductions in cerebral blood flow. We tested the hypothesis that the respiratory-induced alkalosis is associated with lower circulating microvesicle concentrations, specifically in the brain, despite the reductions in blood flow. At core temperature + 2°C with respiratory alkalosis, microvesicles derived from endothelial cells, monocytes and leucocytes were at concentrations similar to baseline in the arterial and cerebral venous circulation, with no changes in cross-brain microvesicle kinetics. However, when core temperature was increased by 2°C with CO2 /pH normalized to resting levels, there was a marked cerebral uptake of microvesicles derived from endothelial cells and monocytes. The CO2 /pH-mediated alteration in cerebral microvesicle uptake occurred only in hyperthermia. These new findings suggest that the heat-induced hyperventilatory response might serve a beneficial role by preventing potentially inflammatory microvesicle uptake in the brain.

Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023.

The respiratory system plays an integral part in maintaining acid-base homeostasis. Normal ventilation participates in the maintenance of an open buffer system, allowing for excretion of CO2 produced from the interaction of nonvolatile acids and bicarbonate. Quantitatively of much greater importance is the excretion of CO2 derived from volatile acids produced from the complete oxidation of fat and carbohydrate. A primary increase in CO2 tension of body fluids is the cause of respiratory acidosis and develops most commonly from one or more of the following: (1) disorders affecting gas exchange across the pulmonary capillary, (2) disorders of the chest wall and the respiratory muscles, and/or (3) inhibition of the medullary respiratory center. Respiratory alkalosis or primary hypocapnia is most commonly caused by disorders that increase alveolar ventilation and is defined by an arterial partial pressure of CO2 <35 mm Hg with subsequent alkalization of body fluids. Both disorders can lead to life-threatening complications, making it of paramount importance for the clinician to have a thorough understanding of the cause and treatment of these acid-base disturbances.

Rocuronium action can be affected by hyperventilation: a case report and computational simulation.

The neuromuscular blocking potency of rocuronium varies with respiratory pH changes, increasing at lower pH and decreasing at higher pH; thus, hyperventilation-induced respiratory alkalosis is expected to decrease the potency of rocuronium. We report a case of anesthetic management of modified electroconvulsive therapy (m-ECT) for a patient monitored with electromyography-based neuromuscular monitoring during two patterns of ventilation to elucidate their relationship and propose the possible mechanisms underlying the effects by computational simulations. Case presentation: The patient was a 25-year-old man with schizophrenia. In m-ECT, hyperventilation may be used to produce longer seizures. We compared the neuromuscular monitoring data recorded during hyperventilation and during normal ventilation while receiving the same dose of rocuronium. Despite receiving the same dose of rocuronium, the time required for the first twitch to decrease to 80% of the control value was delayed in hyperventilation compared to normal ventilation. Conclusions: This case report and computational simulation suggest that respiratory alkalosis might delay the action of rocuronium. It is necessary to consider the delayed action of rocuronium when hyperventilation is performed.

Spectrum of Disorders associated with Tetany.

INTRODUCTION: Awareness regarding the etiological spectrum of tetany is poor among physicians. Because of poor awareness, tetany is underdiagnosed and undertreated. MATERIALS AND METHODS: Databases like PubMed, PubMed Central, Scopus, and Google Scholar are searched to identify peer-reviewed articles on tetany. Case reports, case series, and original articles are analyzed to identify different causes of tetany prevalent in the community. Different causes found are analyzed and tabulated, and finally, a flowchart is made on the approach for diagnosing different underlying pathologies of tetany. RESULTS: Both metabolic and respiratory alkalosis are important causes of tetany because of reduced ionized calcium levels. Gitelman syndrome (GS) is associated with metabolic alkalosis, hypokalemia, hypomagnesemia and hypocalciuria, and frequently causes normocalcemic tetany. Recurrent vomiting and primary hyperaldosteronism also cause tetany due to metabolic alkalosis. Hyperventilation syndrome (HVS) leads to respiratory alkalosis and is a frequent cause of tetany. Hyperventilation-induced tetany is also seen after spinal anesthesia and in respiratory disorders like asthma. Vitamin D deficiency (VDD), primary hypoparathyroidism, and pseudohypoparathyroidism (PHP) (1a, 1b, and 2) cause hypocalcemic tetany. Hypomagnesemia causes hypocalcemia and tetany due to peripheral parathyroid hormone resistance and impaired parathyroid hormone secretion. Drugs causing tetany include bisphosphonates, denosumab, cisplatin, antiepileptics, aminoglycosides, diuretics, etc. Tetany is also seen in acute pancreatitis, dengue, falciparum malaria, hyperemesis gravidarum, tumor lysis syndrome (TLS), massive blood transfusion, etc. Conclusion: The spectrum of disorders associated with tetany is diverse. Awareness of different causes will help early and proper diagnosis of tetany.

[Severe respiratory alkalosis due to psychogenic hyperventilation. Report of one case]. / Alcalosis respiratoria grave, la transformación de un cuadro funcional en orgánico. Caso clínico.

Severe respiratory alkalosis is a life-threatening condition, as it induces hypo- calcaemia and extreme adrenergic sensitivity leading to cerebral and myocardial vasoconstriction. We report a 37-year-old woman with previous consultations for a conversion disorder. While she was infected with SARS-CoV-2 (without pulmonary involvement), she consulted in the emergency room due to panic attacks. On admission, she developed a new conversion crisis with progressive clinical deterioration, hyperventilation, and severe respiratory alkalosis (pH 7.68, Bicarbonate 11.8 mEq/L and PaCO2 10 mmHg). Clinically, she was in a coma, with respiratory and heart rates 55 and 180 per min, a blood pressure of 140/90 mmHg, impaired perfusion (generalized lividity, distal coldness, and severe skin mottling) and tetany. She also had electrocardiographic changes and high troponin levels suggestive of ischemia, and hyperlactatemia. She was managed in the hospital with intravenous benzodiazepines. The clinical and laboratory manifestations resolved quickly, without the need for invasive measures and without systemic repercussions.

Bidirectional ventricular tachycardia induced by respiratory alkalosis mediated hypokalemia in a patient with acute ischemic heart failure.

Bidirectional ventricular tachycardia (BVT) is a rare arrhythmia that is generally observed in patients with catecholaminergic ventricular tachycardia or digoxin overdose. Herein, we present a case of BVT and electrical storm (ES) in an acute ischemic heart failure patient that is typically induced by hypokalemia. The patient was in invasive mechanical ventilator (MV) support and hypokalemia was related to acute respiratory alkalosis and that caused refractory hypokalemia despite intravenous (IV) potassium replacement. We also discuss our approach to solve refractory hypokalemia caused by respiratory alkalosis.

Changes in acid-base status in oxygen toxicity at 230 kPa oxygen as a function of exposure time.

Breathing less than 50 kPa of oxygen over time can lead to pulmonary oxygen toxicity (POT). Vital capacity (VC) as the sole parameter for POT has its limitations. In this study we try to find out the changes of acid-base status in a POT rat model. Fifty male rats were randomly divided into five groups, exposed to 230 kPa oxygen for three, six, nine and 12 hours, respectively. Rats exposed to air were used as controls. After exposure the mortality and behavior of rats were observed. Arterial blood samples were collected for acid-base status detection and wet-dry (W/D) ratios of lung tissues were tested. Results showed that the acid-base status in rats exposed to 230 kPa oxygen presented a dynamic change. The primary status was in the compensatory period when primary respiratory acidosis was mixed with compensated metabolic alkalosis. Then the status changed to decompensated alkalosis and developed to decompensated acidosis in the end. pH, PCO2, HCO3-, TCO2, and BE values had two phases: an increase and a later decrease with increasing oxygen exposure time, while PaO2 and lung W/D ratio showed continuously increasing trends with the extension of oxygen exposure time. Lung W/D ratio was significantly associated with PaO2 (r = 0.6385, p = 0.002), while other parameters did not show a significant correlation. It is concluded that acid-base status in POT rats presents a dynamic change: in the compensatory period first, then turns to decompensated alkalosis and ends up with decompensated acidosis status. Blood gas analysis is a useful method to monitor the development of POT.

Cerebral metabolism, oxidation and inflammation in severe passive hyperthermia with and without respiratory alkalosis.

KEY POINTS: It was unknown whether respiratory alkalosis impacts the global cerebral metabolic response as well as the cerebral pro-oxidation and inflammatory response in passive hyperthermia. This study demonstrated that the cerebral metabolic rate was increased by ∼20% with passive hyperthermia of up to +2°C oesophageal temperature, and this response was unaffected by respiratory alkalosis. Additionally, the increase in cerebral metabolism did not significantly impact the net cerebral release of oxidative and inflammatory markers. These data indicate that passive heating of up to +2°C core temperature in healthy young men is not enough to confer a major oxidative and inflammatory burden on the brain, but it does markedly increase the cerebral metabolic rate, independently of PaCO2 . ABSTRACT: There is limited information concerning the impact of arterial PCO2 /pH on heat-induced alteration in cerebral metabolism, as well as on the cerebral oxidative/inflammatory burden of hyperthermia. Accordingly, we sought to address two hypotheses: (1) passive hyperthermia will increase the cerebral metabolic rate of oxygen (CMRO2 ) consistent with a combined influence of Q10 and respiratory alkalosis; and (2) the net cerebral release of pro-oxidative and pro-inflammatory markers will be elevated in hyperthermia, particularly in poikilocapnic hyperthermia. Healthy young men (n = 6) underwent passive heating until an oesophageal temperature of 2°C above resting was reached. At 0.5°C increments in core temperature, CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-jugular venous oxygen content difference (cannulation). Net cerebral glucose/lactate exchange, and biomarkers of oxidative and inflammatory stress were also measured. At +2.0°C oesophageal temperature, arterial PCO2 was restored to normothermic values using end-tidal forcing. The primary findings were: (1) while CMRO2 was increased (P < 0.05) by ∼20% with hyperthermia of +1.5-2.0°C, this was not influenced by respiratory alkalosis, and (2) although biomarkers of pro-oxidation and pro-inflammation were systemically elevated in hyperthermia (P < 0.05), there were no differences in the trans-cerebral exchange kinetics. These novel data indicate that passive heating of up to +2°C core temperature in healthy young men is not enough to confer a major oxidative and inflammatory burden on the brain, despite it markedly increasing CMRO2 , irrespective of arterial pH.

Mechanisms of acid-base regulation following respiratory alkalosis in red drum (Sciaenops ocellatus).

Respiratory acidosis and subsequent metabolic compensation are well-studied processes in fish exposed to elevated CO2 (hypercapnia). Yet, such exposures in the marine environment are invariably accompanied by a return of environmental CO2 to atmospheric baselines. This understudied phenomenon has the potential to cause a respiratory alkalosis that would necessitate base excretion. Here we sought to explore this question and the associated physiological mechanisms that may accompany base excretions using the red drum (Sciaenops ocellatus). As expected, when high pCO2 (15,000 µatm CO2) acclimated red drum were transferred to normal pCO2, their net H+ excretion shifted from positive (0.157 ± 0.044 µmol g-1 h-1) to negative (-0.606 ± 0.116 µmol g-1 h-1) in the 2 h post-transfer period. Net H+ excretion returned to control rates during the 3 to 24 h flux period. Gene expression and enzyme activity assays demonstrated that while the acidosis resulted in significant changes in several relevant transporters, no significant changes accompanied the alkalosis phase. Confocal microscopy was used to assess alkalosis-stimulated translocation of V-type H+ ATPase to the basolateral membrane previously seen in other marine species; however, no apparent translocation was observed. Overall, these data demonstrate that fluctuations in environmental CO2 result in both acidic and alkalotic respiratory disturbances; however, red drum maintain sufficient regulatory capacity to accommodate base excretion. Furthermore, this work does not support a role for basolateral VHA translocation in metabolic compensation from a systemic alkalosis in teleosts.

Spontaneous Hyperventilation in Severe Traumatic Brain Injury: Incidence and Association with Poor Neurological Outcome.

BACKGROUND: Hypocapnia induces cerebral vasoconstriction leading to a decrease in cerebral blood flow, which might precipitate cerebral ischemia. Hypocapnia can be intentional to treat intracranial hypertension or unintentional due to a spontaneous hyperventilation (SHV). SHV is frequent after subarachnoid hemorrhage. However, it is understudied in patients with severe traumatic brain injury (TBI). The objective of this study was to describe the incidence and consequences on outcome of SHV after severe TBI. METHODS: We conducted a retrospective, observational study including all intubated TBI patients admitted in the trauma center and still comatose 24 h after the withdrawal of sedation. SHV was defined by the presence of at least one arterial blood gas (ABG) with both PaCO2 < 35 mmHg and pH > 7.45. Patient characteristics and outcome were extracted from a prospective registry of all intubated TBI admitted in the intensive care unit. ABG results were retrieved from patient files. A multivariable logistic regression model was developed to determine factors independently associated with unfavorable outcome (defined as a Glasgow Outcome Scale between 1 and 3) at 6-month follow-up. RESULTS: During 7 years, 110 patients fully respecting inclusion criteria were included. The overall incidence of SHV was 69.1% (95% CI [59.9-77]). Patients with SHV were more severely injured (median head AIS score (5 [4-5] vs. 4 [4-5]; p = 0.016)) and exhibited an elevated morbidity during their stay. The proportion of patients with an unfavorable functional neurologic outcome was significantly higher in patients with SHV: 40 (52.6%) versus 6 (17.6%), p = 0.0006. After adjusting for confounders, SHV remains an independent factor associated with unfavorable outcome at the 6-month follow-up (OR 4.1; 95% CI [1.2-14.4]). CONCLUSIONS: SHV is common in patients with a persistent coma after a severe TBI (overall rate: 69%) and was independently associated with unfavorable outcome at 6-month follow-up.

The effect of inspiratory muscle fatigue on acid-base status and performance during race-paced middle-distance swimming.

The aim of this study was to investigate the effect of pre-induced inspiratory muscle fatigue (IMF) on race-paced swimming and acid-base status. Twenty-one collegiate swimmers performed two discontinuous 400-m race-paced swims on separate days, with (IMF trial) and without (control trial) pre-induced IMF. Swimming characteristics, inspiratory and expiratory mouth pressures, and blood parameters were recorded. IMF and expiratory muscle fatigue (P < 0.05) were evident after both trials and swimming time was slower (P < 0.05) from 150-m following IMF inducement. Pre-induced IMF increased pH before the swim (P < 0.01) and reduced bicarbonate (P < 0.05) and the pressure of carbon dioxide (PCO2) (P < 0.05). pH (P < 0.05), bicarbonate (P < 0.01) and PCO2 (P < 0.05) were lower during swimming in the IMF trial. Blood lactate was similar before both trials (P > 0.05) but was higher (P < 0.01) in the IMF trial after swimming. Pre-induced IMF induced respiratory alkalosis, reduced bicarbonate buffering capacity and slowed swimming speed. Pre-induced and propulsion-induced IMF reflected metabolic acidosis arising from dual role breathing and propulsion muscle fatigue.

Leigh syndrome in individuals bearing m.9185T>C MTATP6 variant. Is hyperventilation a factor which starts its development?

Leigh syndrome (LS), subacute necrotizing encephalomyelopathy is caused by various genetic defects, including m.9185T>C MTATP6 variant. Mechanism of LS development remains unknown. We report on the acid-base status of three patients with m.9185T>C related LS. At the onset, it showed respiratory alkalosis, reflecting excessive respiration effort (hyperventilation with low pCO2). In patient 1, the deterioration occurred in temporal relation to passive oxygen therapy. To the contrary, on the recovery, she demonstrated a relatively low respiratory drive, suggesting that a "hypoventilation" might be beneficial for m.9185T>C carriers. As long as circumstances of the development of LS have not been fully explained, we recommend to counteract hyperventilation and carefully dose oxygen in patients with m.9185T>C related LS.

Metabolic Acidosis or Respiratory Alkalosis? Evaluation of a Low Plasma Bicarbonate Using the Urine Anion Gap.

Hypobicarbonatemia, or a reduced bicarbonate concentration in plasma, is a finding seen in 3 acid-base disorders: metabolic acidosis, chronic respiratory alkalosis and mixed metabolic acidosis and chronic respiratory alkalosis. Hypobicarbonatemia due to chronic respiratory alkalosis is often misdiagnosed as a metabolic acidosis and mistreated with the administration of alkali therapy. Proper diagnosis of the cause of hypobicarbonatemia requires integration of the laboratory values, arterial blood gas, and clinical history. The information derived from the urinary response to the prevailing acid-base disorder is useful to arrive at the correct diagnosis. We discuss the use of urine anion gap, as a surrogate marker of urine ammonium excretion, in the evaluation of a patient with low plasma bicarbonate concentration to differentiate between metabolic acidosis and chronic respiratory alkalosis. The interpretation and limitations of urine acid-base indexes at bedside (urine pH, urine bicarbonate, and urine anion gap) to evaluate urine acidification are discussed.

The venous-arterial difference in CO2 should be interpreted with caution in case of respiratory alkalosis in healthy volunteers.

The venous-arterial difference in CO2 (ΔCO2) has been proposed as an index of the adequacy of tissue perfusion in shock states. We hypothesized that the variation in PaCO2 (hyper- or hypocapnia) could impact ΔCO2, partly through microcirculation adaptations. Fifteen healthy males volunteered to participate. For hypocapnia condition (hCO2), the subjects were asked to hyperventilate, while they were asked to breathe a gas mixture containing 8 % CO2 for hypercapnia condition (HCO2). The 2 conditions were randomly assigned. Blood gases were measured at baseline before each condition, and after 5-7 min of either hCO2 or HCO2 condition. Microcirculation was assessed by the muscle reoxygenation slope measured with near infrared spectroscopy following a vascular occlusion test and by skin circulation with in vivo reflectance confocal microscopy. ΔCO2 was significantly increased with hCO2 while it tended to decrease with HCO2 (non-significant). HCO2 induced a moderate increase of the resaturation slope of NIRS oxygenation. Skin microcirculatory blood flow significantly dropped with hCO2, while it remained unchanged with hypercapnia. Our results warrant cautious interpretation of ΔCO2 as an indicator of tissue perfusion during respiratory alkalosis.

Hypoxia silences retrotrapezoid nucleus respiratory chemoreceptors via alkalosis.

In conscious mammals, hypoxia or hypercapnia stimulates breathing while theoretically exerting opposite effects on central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory consequences of Arch activation (10 s) in conscious rats during normoxia, hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non-REM sleep and quiet wake. Compared with normoxia, the breathing frequency reduction (Δf(R)) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2, and absent in 12% FiO2. Tidal volume changes (ΔV(T)) followed the same trend. The effect of hypoxia on Δf(R) was not arousal-dependent but was reversed by reacidifying the blood (acetazolamide; 3% FiCO2). Δf(R) was highly correlated with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1 neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic breathing about equally during both sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN neurons are silent above pHa 7.5 and increasingly active below this value. During hyperoxia, RTN activation maintains breathing despite the inactivity of the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation increases breathing frequency via pathways that bypass RTN.

A Case of Salicylate Intoxication Complicated by Coagulopathy, Pulmonary Edema, and Pancreatitis.

The large availability of salicylic acid products makes them an often encountered source of poisoning in the emergency department. Even though in most cases the prognosis is good, with a low incidence of long-term morbidity and mortality, complications do occur, and some of those can be life threatening. We present an unusual case of salicylate intoxication in an adolescent in which several uncommon complications (severe coagulopathy, pulmonary edema, and pancreatitis) conjoined together. We review the literature and discuss the complications pathogenesis and differential diagnosis. We suggest that these potentially life-threatening complications be acknowledged, investigated, and rapidly treated.