Respiratory alkalosis is one of many acid-base disorders found among critically ill patients. It is detected by arterial blood gas analysis and electrolyte levels. To diagnose respiratory alkalosis or assess the severity of the condition, the physician must understand clinical acid-base balance. Alkalosis, by definition, is a pathologic state that causes or tends to cause an increase in blood pH. Hence, one can have an alkalosis with normal pH if compensation has occurred; alkalemia is defined as a blood pH above 7.45. The term respiratory in respiratory alkalosis refers to the primary respiratory mechanism responsible for the change.[1]
Hypocapnia (low PCO2) develops whenever CO2 elimination by the lungs exceeds tissue production. One or more of three basic categories usually underlie respiratory alkalosis: hypoxia, pulmonary diseases, and CNS disorders[2] (see image below).
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Pediatric Respiratory Alkalosis. Schematic presentation of pathophysiology of hyperventilation.
Compensation
In respiratory acid-base disturbances, changes in ventilation, and hence PCO2, represent the primary disturbance, and compensation occurs by alterations in plasma bicarbonate.
In chronic respiratory alkalosis, increased urinary bicarbonate excretion resists the pH change caused by hypocapnia. This renal compensation begins within several hours and takes several days for the maximal response.
In acute respiratory alkalosis, an initial small decrease may occur in plasma bicarbonate concentration because of chemical mass action.[3] Hypocapnia leads to increased formation of carbonic acid, to lowered plasma hydrogen ion concentration (alkalemia), and to concomitant reduced plasma bicarbonate concentration. This is quantitatively less profound than renal compensation and is not related to change in bicarbonate excretion.[4]
Formulas for estimating appropriate compensation in simple respiratory alkalosis (limit of compensation is [HCO3-] of approximately 15) include the following:
Acute alkalosis - Change in pH = (change in PCO2) X 0.08
Chronic alkalosis - Change in pH = (change in PCO2) X 0.003
Any condition associated with a fall in the PaO2 below 55 mm Hg or with decreased oxygen delivery to the tissues increases minute ventilation, causing respiratory alkalosis. Causes include the following:
Altitude/low fraction of inspired oxygen (FIO2)
Anemia
Hypotension
Lung disease
Pulmonary disorders
Interstitial, airway, and parenchymal pulmonary diseases affect PO2 more prominently than PCO2, and hyperventilation usually results in hypocapnia.[2] Inflammation of the irritant receptors in the airways and parenchyma also causes hyperventilation, resulting in respiratory alkalosis. Causes include the following:
Edema (hydrostatic or permeability)
Embolism
Airway obstruction/inflammation
Pneumonia: A classic presentation of Pneumocystis pneumonia is hypoxemia with respiratory alkalosis.
Interstitial lung disease
Mechanical ventilation
Respiratory alkalosis could result from a ventilatory rate or tidal volume that is too high or from the patient triggering excessive additional breaths.
Extrapulmonary disorders
In these cases, the child has normal lung function with an overriding ventilatory stimulus. These disorders usually result in the most severe respiratory alkalosis. Causes include the following:
Liver failure, especially with hepatic encephalopathy: Guidelines have been established for the management of acute liver failure, although these are primarily focused on adult patients with hepatic failure.[6]
Patients primarily have clinical manifestations of the disorder causing the respiratory alkalosis[7] ; the effects of respiratory alkalosis per se are fewer.
Acute respiratory alkalosis has more intense features than chronic respiratory alkalosis because later renal compensation and cellular adaptation minimize the pH change.
Alkalosis, by promoting the binding of calcium to albumin, can reduce the fraction of ionized calcium in blood, causing tetany. Symptomatic hypocalcemia is more common with respiratory alkalosis than with metabolic alkalosis.
Patients have symptoms of underlying disorders.
Rapid decrease in PCO2 can result in dizziness, mental confusion, and (rarely) seizures,[8] even with a PO2 that is within the reference range. This is probably due to the cerebral vasoconstriction caused by the hypocarbia.
The major complication of respiratory alkalosis per se is the concomitant hypocalcemia and potential for tetany. Patients may have tetany due to reduced ionized calcium in blood.
Patients have fever if respiratory alkalosis is the result of an infectious disorder.
Hyperthermia of any origin may, in turn, result in respiratory alkalosis.
Acute respiratory alkalosis may cause mild tachycardia.
The respiratory rate is usually high.[9] In some cases, the hyperventilation is primarily a manifestation of increased tidal volume and the respiratory rate may not be markedly elevated. This is often observed in the respiratory alkalosis compensating diabetic ketoacidosis.
Blood pressure is usually maintained, except when respiratory alkalosis is caused by massive pulmonary embolism or sepsis.
Central Nervous System
CNS effects are secondary to the reduction in cerebral blood flow (CBF) caused by reduction in PCO2. CBF may decrease by 1-2 mL/100 g/min for each 1 mm Hg fall in PCO2, with maximum reduction in CBF of 40-50% achieved with a PCO2 of 20-25 mm Hg. Reduced CBF may cause altered mentation, dizziness, and sometimes seizures.
The effects of hyperoxemia and hypoxemia on CBF velocity in premature neonates appear to depend on gestational age.[10]
Cardiovascular system
Cardiovascular effects of acute hypocapnia are minimal in patients who are awake. Tachycardia may be the only observable manifestation.
Electrolyte imbalance resulting from respiratory alkalosis may very rarely induce dysrhythmias, although only in patients with underlying heart disease.
A simple step-wise approach proves useful for further workup in patients with respiratory alkalosis, such as the following:
Step 1: Prove the presence of respiratory alkalosis by an ABG. A PCO2 less than 35 indicates alveolar hyperventilation. A pH greater than 7.4 is highly suggestive of alkalosis. When both are found, respiratory alkalosis is likely.
Step 2: Assess the chronicity of hyperventilation. Reference range HCO3- with a pH greater than 7.45 suggests acute hyperventilation, whereas low HCO3- with a pH of 7.4-7.45 suggests a chronic partially compensated process.
Step 3: An arterial-alveolar oxygen gradient within the reference range and a pH greater than 7.4 is consistent with hyperventilation secondary to direct CNS stimulation, with normal lung function.
Step 4: Arterial pH less than 7.4 is usually observed with alveolar hyperventilation as compensation for metabolic acidosis (overcompensation for metabolic acidosis is very rare).
Step 5: Respiratory alkalosis is likely with hypoxemia with alveolar hyperventilation. However, determining if the alkalosis is caused by the hypoxia or if the hypoxia and the alkalosis are caused by the underlying pulmonary disease is difficult.
Measurement of arterial pH, HCO3-, and PCO2 are crucial. Transcutaneous or end-tidal PCO2 may be used in place of arterial PCO2; however, transcutaneous PCO2 requires normal skin perfusion, and end-tidal pCO2 is useful only in the presence of normal lung function and when no other acid-base disturbance is suspected. Furthermore, the noninvasive tests do not measure the pH.
A detailed history and careful physical examination should indicate an underlying disorder.
Standard nomograms (see image below) help diagnose simple acid-base disorders, despite the following limitations:
They describe acid-base status in children with a steady-state condition. Hence, nomograms are not helpful for patients with rapidly changing status.
Nomograms lose precision at extremes.
Values falling in respiratory alkalosis may overlap with other mixed disorders and ultimately require clinical judgment.
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Pediatric Respiratory Alkalosis. Acid-base nomogram shows confidence bands for simple acid-base disturbances. Conversion factor is 1 torr = 0.13 kPa.
Hyperventilation syndrome is often considered a diagnosis of exclusion. Physicians must consider other causes before making the diagnosis. However, in the typical patient with a normal alveolar-arterial oxygen gradient with an acute stress, the diagnosis can be made with confidence.
Imaging studies are not necessarily indicated for the diagnosis of respiratory alkalosis but may be indicated for the diagnosis of the underlying etiology.
Chest radiography may be indicated.
Ventilation/perfusion imaging, helical chest CT imaging, or CT angiography may be performed if pulmonary embolism is suspected.
CT imaging or MRI of the brain may be indicated if CNS pathology is suspected.
Care in patients with respiratory alkalosis is primarily directed to the underlying etiology.
Respiratory alkalosis is rarely life threatening. Direct measures to correct it are usually unnecessary and often may not work unless the underlying cause is treated. The prognosis relates to the underlying pathology.
Respiratory alkalosis encountered during mechanical ventilation may be corrected by reducing the rate or the tidal volume or using sedation and paralysis (if it is caused by patient-triggered ventilator breaths).
Patients with hyperventilation syndrome may be immediately relieved by rebreathing into a small-volume paper bag; then, the physician should address treating the patient's psychological stress.
Drug therapy for respiratory alkalosis is directed toward alleviation of the underlying causative disorder.
Girish G Deshpande, MD, MBBS, FAAP, Associate Professor of Pediatrics, Interim Director and Division Chief of Critical Care Medicine, Department of Pediatrics, University of Illinois College of Medicine at Peoria; Consulting Staff, Division of Critical Care Medicine, Children's Hospital of Illinois at OSF St Francis Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Barry J Evans, MD, Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children's Medical Center
Disclosure: Nothing to disclose.
Chief Editor
Girish D Sharma, MD, FCCP, FAAP, Professor of Pediatrics, Rush Medical College; Director, Section of Pediatric Pulmonology and Rush Cystic Fibrosis Center, Rush Children's Hospital, Rush University Medical Center
Disclosure: Nothing to disclose.
Additional Contributors
G Patricia Cantwell, MD, FCCM, Professor of Clinical Pediatrics, Chief, Division of Pediatric Critical Care Medicine, University of Miami Leonard M Miller School of Medicine/ Holtz Children's Hospital, Jackson Memorial Medical Center; Medical Director, Palliative Care Team, Holtz Children's Hospital; Medical Manager, FEMA, South Florida Urban Search and Rescue, Task Force 2
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