Mixed Respiratory Alkalosis Research Articles

PSEUDOHYPOALDOSTERONISM TYPE I IN PATIENT ADMITTED WITH NEONATAL ABSTINENCE SYNDROME: A CASE REPORT AND REVIEW OF LITERATURE

Pseudohypoaldosteronism (PHA) type 1 is a rare genetic disorder affecting one in 47,000-80,000 newborns. An autosomal dominant type which is restricted to the kidney (also known as rPHA1) and an autosomal recessive type which is more severe and presents with systemic symptoms were reported. A 3-h-old male infant was admitted to the neonatology ward due to high pitch cries, jitteriness, mild tremors, and excessive sleep with a positive history of maternal addiction. For the 1st time, after 9 days, the infant developed hyperkalemia (7 mEq/L) with mixed respiratory alkalosis, and metabolic acidosis (PH: 7.42, Pco2: 22 mm-Hg, Hco3: 12 mmol/L) and blood pressures of 84/44 mm-Hg were recorded. Even after initial treatment, once again the patient developed hyperkalemia resistant to therapy. Hyponatremia was also noted. Hormonal assays were collected, and congenital adrenal hyperplasia (a common differential diagnosis in neonatal hyperkalemia) was ruled out. Elevated renin and aldosterone levels were reported. On the 20th day, hyperkalemia-induced cardiac arrhythmia was demonstrated in the 2nd lead (K+ - 7.5 mEq/L). We report that this case as PHA type 1 is the rare but life-threatening cause of neonatal hyperkalemia. Initial therapy can prevent the possible occurrence of sudden death. Key words: Hyperkalemia, Hypernatremia, Neonate, Pseudohypoaldosteronism type 1

Carboxyhemoglobinemia and Methemoglobinemia in an Atypical Case of Salicylate Toxicity: A Potentially Hidden Association

We report an atypical case of salicylate toxicity in a child without a reported exposure to aspirin, who presented with coexisting methemoglobinemia and carboxyhemoglobinemia, and provide mechanistic theories as to the potential pathway by which salicylates can lead to such dyshemoglobinemias. The patient, a 17-month old male, presented to the hospital 10 h after six episodes of vomiting, tachypnea and hyperpnea. Laboratory values showed a mixed respiratory alkalosis and metabolic acidosis; however, the parent’s denial of aspirin exposure, coupled with laboratory results indicating carboxyhemoglobinemia, methemoglobinemia and neutrophilic leukocytosis, disguised a toxic salicylate level of 51.1 mg/dL. We searched the PubMed database for sources of salicylate exposure using the terms: “salicylate exposure”, “salicylate toxicity”, “sources”, and an association of salicylates with carboxyhemoglobinemia methemoglobinemia using those three terms. Furthermore, Google Scholar and PubMed were used to search for biochemical literature explaining the association of salicylates with red blood cell oxidation, methemoglobin and carbon monoxide formation. We discovered that the mechanism by which high dose salicylates lead to carboxyhemoglobinemia and methemoglobinemia had not been previously described. We propose that salicylates in high doses can induce a methemoglobinemia through increased vascular release of nitric oxide through induction of IL-1β and carboxyhemoglobinemia via lipid peroxidation, leading to the release of carbon monoxide.

Acid-base disturbances in acute poisoning and their association with survival

PurposeThe purpose was to investigate the association between acid-base disturbances and mortality in acute poisoning. Materials and methodsWe performed a retrospective cross-sectional exploratory study on all acutely poisoned patients older than 12 years who had been admitted to the main tertiary toxicology hospital in Tehran between March and August 2010. ResultsOf a total of 1167 patients (median age=25 years, 50.9% male), 98 died (74.5% male). Psychotropic medications were the most common cause of poisoning (36.5%), whereas narcotics and psychodysleptics were the most common cause of death (23.5%). Mixed respiratory alkalosis and metabolic acidosis with normal pH were the most common acid-base status (333, 28.5%). However, patients with primary metabolic acidosis and respiratory compensation had significantly higher mortality (31 cases, 18.8%). Logistic regression analysis identified age (odds ratio [OR], 1.051; 95% confidence interval [CI], 1.031-1.070; P<.001), intensive care unit admission (OR, 12.405; 95% CI, 7.178-21.440; P<.001), consciousness level (OR, 1.752; 95% CI, 1.301-2.359; P<.001), hospitalization period (OR, 1.1361; 95% CI, 1.079-1.195; P<.001), severe metabolic acidosis (OR, 6.016; 95% CI, 1.647-21.968; P=.007), and primary respiratory alkalosis (OR, 5.579; 95% CI, 1.353-23.001; P=.017) as death predictors during hospitalization (P<.001). ConclusionOn-arrival acid-base status predicts survival and can be used in prognostication of the poisoned patients.

Mixed Acid-Base Abnormality in a Patient with Herbicide Poisoning - Possible Insights on the Mechanism of Toxicity

2, 4-Diclorophenoxyacetic acid (2, 4-D), a herbicide, is an uncommon cause of intentional poisoning in humans. We report a patient who survived after ingestion of a fatal dose of 2, 4-D and explore possible mechanisms for the observed metabolic abnormalities. A 48-year-old male was brought following ingestion of a mixture of 2, 4-D and metribuzin (50-gm each). He presented with vomiting and altered sensorium and required intubation and mechanical ventilation. There was evidence of rhabdomyolysis, non-oliguric renal failure and multiple electrolyte abnormalities. The acid-base abnormalities were consistent with mixed respiratory alkalosis with normal anion gap metabolic acidosis. The patient was treated with supportive care and alkaline diuresis and made an uneventful recovery. The metabolic acidosis was attributed to proximal tubular dysfunction while the respiratory alkalosis with altered conscious state and normal oxygenation suggested central hyperventilation as the mechanisms for the observed metabolic abnormalities with 2, 4-D poisoning.

Acid base imbalances in ill neonatal foals and their association with survival.

Acid-base imbalances observed in human paediatric patients are associated with outcome. Likewise, neonatal foals may have different acid-base imbalances associated with diagnosis or prognosis. To determine acid-base imbalances by the quantitative method in ill neonatal foals and assess their association with diagnosis and prognosis. Observational prospective clinical study. This study included 65 ill neonatal foals (32 septic, 33 nonseptic) admitted to an equine referral hospital from 2005 to 2011with acid-base parameters determined on admission and a control group of 33 healthy neonatal foals. Blood pH, pCO2 , sodium, potassium, chloride, L-lactate, albumin and phosphate concentrations were determined. Bicarbonate, globulin, measured strong ion difference (SIDm ), nonvolatile weak buffer concentrations (Atot ), base excess and its components were calculated. Analysis of covariance (ANCOVA) and multiple linear regression statistical analyses were performed. Results are summarised as mean ± s.d. for normally distributed variables and median [25-75th percentiles] for non-normally distributed ones. A total of 63% of ill foals had respiratory alkalosis and 58.5% had SIDm acidosis. The combination of both alterations was detected in 21 of 65 ill foals and abnormal pH was found in 24 of 65. Compared with healthy foals, ill foals had significantly lower SIDm (nonseptic 31.6 ± 6.3 [P<0.01] and septic 32.0 ± 6.4 [P<0.01] vs. control 40.3 ± 3.1 mmol/l), potassium (nonseptic 3.5 [3.3-3.8; P<0.01] and septic 3.6 [3.2-4.3; P = 0.01] vs. control 4.2 [3.8-4.5] mEq/l) and higher L-lactate (nonseptic 5.1 ± 4.2 [P = 0.01] and septic 5.0 ± 3.7 [P = 0.03] vs. control 2.5 ± 1.3 mmol/l). Significantly higher L-lactate and venous pCO2 were found in nonsurviving (6.4 ± 3.5 mmol/l [P = 0.04] and 51 ± 13 mmHg [P<0.01]) compared with surviving foals. The most common acid-base imbalances observed in ill foals were respiratory alkalosis, SIDm acidosis or mixed respiratory alkalosis with strong ion acidosis. Increased venous pCO2 and blood L-lactate concentration were associated with poor outcome.

Take my breath away: a case of lactic acidosis in an asthma exacerbation

A 36-year-old male with a history of chronic asthma presented to an emergency department with shortness of breath consistent with an asthma exacerbation. He had persistent tachypnea following inhaled bronchodilator treatment; thus, the workup and differential diagnosis were expanded. He was found to have a mixed respiratory alkalosis and metabolic acidosis with elevated serum lactate without an obvious cause and was admitted to hospital. His case was reviewed, and the lactic acidosis was thought to be caused by inhaled β2-agonist use. Emergency physicians should be aware of the potential side effects of inhaled β2-agonists as lactic acidosis may complicate clinical assessment and management of asthma exacerbations and lead to unnecessary and potentially dangerous escalations in therapy.

Respiratory Alkalosis and Metabolic Acidosis in a Child Treated With Sulthiame

To report on severe acid-base disturbance in a child with symptomatic epilepsy treated with sulthiame. A 9.5-year-old boy with chronic generalized tonic-clonic seizures was treated with carbamazepine and valproic acid. Because of poor seizure control, sulthiame was added to the treatment. Two months later, he presented at the emergency department with severe weakness, headache, dizziness, dyspnea, anorexia, and confusional state. Arterial blood gas analysis showed mixed respiratory alkalosis with high anion gap metabolic acidosis. Sulthiame-induced acid-base disturbance was suspected. The drug was withheld for the first 24 hours and then restarted at a reduced dosage. The arterial blood gases gradually normalized, the confusion disappeared, and the patient was discharged home.Three months later, 4 weeks after an increase in sulthiame dosage, the patient was once again admitted with the same clinical picture. Improvement was noted after the drug dosage was reduced. This is the first report of mixed respiratory alkalosis and metabolic acidosis in a child treated with sulthiame. Monitoring of the acid-base status should be considered in patients treated with sulthiame.

The effects of softwater acclimation on respiratory gas transfer in the rainbow trout Oncorhynchus mykiss

Gill O2 uptake, CO2 excretion, ventilation and blood respiratory/acid&shy;base variables were evaluated in control and softwater-acclimated trout (Oncorhynchus mykiss) to test the hypothesis that gill chloride cell (CC) proliferation, elicited by 2 weeks of softwater exposure, impairs the diffusion of respiratory gases across the gill. The proliferation of CCs in softwater fish was verified using light microscopy, and its impact on respiratory gas transfer was assessed in vivo by continuous monitoring of arterial blood PO2 (PaO2), PCO2 (PaCO2) and pH (pHa) using an extracorporeal blood circulation under conditions of normoxia and graded hypoxia [water PO2 (PwO2) was lowered from 20.0 kPa to 5.3 kPa within 20 min]. During normoxia, ventilation frequency was significantly higher in the softwater trout (78&plusmn;4 versus 57&plusmn;4 breaths min-1; mean &plusmn; s.e.m.), while ventilation amplitude was similar in both groups (1.0&shy;1.1 cm opercular displacement). PaCO2 and plasma HCO3- concentration were significantly lower in the softwater fish and the blood acid&shy;base status was characterized by a mixed respiratory alkalosis and metabolic acidosis such that blood pH was not statistically different between the two groups. CO2 excretion (2.5&shy;2.8 mmol kg-1 h-1) and O2 uptake rates (2.3&shy;5.1 mmol kg-1 h-1), as measured during normoxia, were unaffected by acclimation to soft water. During hypoxia, ventilation frequency and amplitude increased in the control trout, whereas only ventilation amplitude increased in the softwater-acclimated fish. The rate of PaO2 reduction during hypoxia was significantly greater in the softwater fish (0.84&plusmn;0.06 versus 0.65&plusmn;0.06 kPa PaO2 kPa-1 PwO2) and, at the most severe level of hypoxia (PwO2=5.3 kPa), PaO2 was significantly lower in the softwater fish. The rate of PaCO2 reduction (caused by hyperventilation) was significantly lower in the softwater-acclimated fish (0.002&plusmn;0.001 versus 0.005&plusmn;0.001 kPa PaCO2 kPa-1 PwO2; mean &plusmn; s.e.m.; P<0.06) and, indeed, was not statistically different from zero. Blood pH did not change significantly during hypoxia in either group but, through much of the hypoxic period (7&shy;15 kPa PwO2), pHa was statistically lower in the softwater-acclimated fish. These results demonstrate that exposure of trout to soft water for 2 weeks is associated with proliferation of lamellar CCs and impaired branchial gas transfer. Hyperventilation was identified as a compensatory physiological adjustment.

Hypocapnia-induced ventilation/perfusion mismatch: a direct CO2 or pH-mediated effect?

The purpose of this study was to determine whether the increased ventilation/perfusion (VA/Q) mismatch caused by hypocapnic hyperventilation in dogs (J. Appl. Physiol. 1993; 74:1306-1314) is a direct CO2 or a pH-mediated effect. From an initial state of hyperventilated respiratory alkalosis (FIO2 = 0.21, VT = 18 ml/kg, RR = 35), we studied the changes in VA/Q distributions, respiratory gas exchange, and hemodynamics when the acid-base status of the dogs was manipulated by combinations of acid or alkali infusion with or without CO2 inhalation. In this manner, we studied respiratory alkalosis (high pH, low PCO2), normalized acid-base status (normal pH, normal PCO2), metabolic acidosis (low pH, normal PCO2), metabolic alkalosis (high pH, normal PCO2), and a mixed respiratory alkalosis and metabolic acidosis (normal pH, low PCO2). Gas exchange was evaluated using the multiple inert gas elimination technique. PaO2 was reduced and VA/Q heterogeneity was increased in all conditions defined by a high pH, independent of the PCO2 (respiratory alkalosis and metabolic alkalosis). In contrast, PaO2 and VA/Q heterogeneity was unchanged in conditions defined by either a normal or low pH (normalized acid-base status, mixed respiratory alkalosis and metabolic acidosis, and metabolic acidosis). Therefore, we conclude that hypocapnia-induced VA/Q mismatch in hyperventilated dogs is pH-mediated and is not a function of PCO2 per se.

Effects of extreme pH on the physiology of the Australian 'yabby' Cherax destructor: acute and chronic changes in haemolymph carbon dioxide, acid-base and ionic status

Freshwater habitats throughout the world are becoming increasingly threatened by the likelihood of acidification, but little consideration has been given to the importance of severe alkalization. Acute and chronic fluctuations in haemolymph acid&shy;base status (PCO2, CCO2 and pH), [Na+] and [Ca2+] were monitored for up to 504 h (21 days) in the Australian freshwater crayfish Cherax destructor exposed to low- and high-pH water. The importance of carapace [Ca2+] during acid exposure was assessed. Crayfish were exposed to pH 7.1, pH 4.5 and pH 8.0 water containing calcium at 500 &micro;mol l-1 while the effect of a lower calcium concentration (50 &micro;mol l-1) was assessed in pH 4.5 water. Cherax in acid water containing 50 &micro;mol l-1 Ca2+ exhibited a significant decrease in CO2 content after 2 h (mean decrease 1.13 mmol l-1, venous; 1.57 mmol l-1, arterial) and large ranges in PCO2 throughout the treatment (2.4&shy;7.3 mmHg). The overall acid&shy;base response was a metabolic acidosis compensated by a respiratory alkalosis. The haemolymph Na+ concentration in both control (pH 7.1, 50 &micro;mol l-1) and acid-exposed animals in lower-Ca2+ water was up to 50 % reduced compared with that in animals in pH 7.1, 500 &micro;mol l-1 Ca2+ water. Ion regulatory mechanisms, causing a subsequent increase in haemolymph [Na+] after 288 h, were implicated as an important component in acid&shy;base homeostasis. Crayfish in acid, low-Ca2+ water also exhibited a 3.2 mmol l-1 increase in haemolymph [Ca2+] and showed a haemolymph alkalosis compared with animals in acid water with higher [Ca2+]. At higher water [Ca2+] in pH 4.5 water (500 &micro;mol l-1 Ca2+), the haemolymph pH of Cherax was only 0.1 unit lower than that of animals in 50 &micro;mol l-1 Ca2+ acid water after 96 h, and both CaCO2 and CvCO2 were unchanged compared with the initial condition. As with low-Ca2+ acid-exposure, the potential haemolymph acidosis appeared largely to be compensated by respiratory alkalosis. There was a transient 31 % reduction in haemolymph [Na+], although osmolality was unchanged (control 411&plusmn;7.29 mosmol kg-1). Acid&shy;base equilibrium recovered rapidly, probably in association with changes in ion flux and the re-establishment of normal haemolymph Na+ concentration. Alkaline-exposed Cherax destructor exhibited a mixed respiratory alkalosis and metabolic acidosis. Whereas haemolymph [Ca2+] increased by 1.8 mmol l-1 after only 1 h, haemolymph Na+ levels increased by 36 % after 2 h, possibly as part of a net H+ loss from the haemolymph. Increased HCO3-/Cl- exchange could contribute to the 4.3 mmol l-1 decrease in haemolymph CO2 level after 0.5 h of alkaline exposure. The responses of Cherax to extreme pH are different from those of the European and North American crayfish species studied to date.

Ketosis, a complication of theophylline toxicity.

A case of prolonged theophylline toxicity in a young non-diabetic female is reported. Blood gas analysis revealed a mixed respiratory alkalosis and metabolic acidosis. The metabolic acidosis was due to ketoacids, which were detected in the patient's breath and urine. The ketones cleared rapidly when theophylline elimination was increased with activated charcoal, i.v. metoprolol reduced excessive b-adrenergic stimulation and a 10% dextrose infusion repleted hepatic glycogen. Theophylline is known to increase free fatty acid levels. It is postulated that prolonged fasting led to depletion of hepatic glycogen and that ketones were generated by metabolism of elevated serum fatty acids. In previous reviews of the metabolic abnormalities associated with theophylline toxicity ketosis has not been described.

The acid-base vector of open-heart surgery.

Fourteen patients submitted to open-heart surgery were studied by serial acid-base and electrolyte determinations in order to demonstrate the sequence and magnitude of disturbances associated with the procedure. Under conditions of the study, including the use of 100 per cent oxygen as the perfusing gas for the oxygenator, respiratory alkalosis develops as the initial change during perfusion but is followed by a "metabolic shift" characterized by falling pH and CO 2 content, while a stable, moderately low pCO 2 is maintained by the oxygenator. The resulting state of mixed respiratory alkalosis and metabolic acidosis changes into a state of relatively pure metabolic acidosis as pCO 2 and bicarbonate content rise while pH falls after perfusion. The factors involved in the "metabolic shift" responsible for development of metabolic acidosis are not identified by this study although length of perfusion, perfusion pressure, and rate of flow are considered as possible factors. Acidosis persists through the early phases of the recovery period but ordinarily resolves without administration of alkali. Serial sampling technics as used in this study may aid in the interpretation of postoperative acidosis, distinguishing between patients who are deteriorating and those who are passing through a transient phase in the process of recovery.