• Minute ventilation (MV) is the volume of all inhaled or exhaled gas in one minute. It is calculated by the multiplication of the tidal volume (V_T) and respiratory rate (RR): MV = V_T × RR.
• During spontaneous ventilation, MV is under tight control by the respiratory center in the brainstem.
  • Central and peripheral feedback mechanisms adjust MV to deliver adequate oxygen to the tissues while removing CO₂ from the lungs.
  • At rest, for an average adult, normal tidal volume is ~500–600 mL (6–8 mL/kg) and the respiratory frequency is around 12–22 breaths per minute. This results in a normal MV of ~7–8 liters per minute.
• Under general anesthesia, the patient can either breathe spontaneously or be mechanically ventilated. Anesthetic agents have dose-dependent effects on the medullary respiratory center that affect MV in both the spontaneously ventilating and postoperative patient.

• MV in the spontaneously ventilating (SV) patient is tightly regulated by the respiratory control center, located in the medulla oblongata. It receives afferent input from mechanoreceptors, chemoreceptors, baroreceptors, and proprioceptors, as well as voluntary control from the cerebral cortex and temperature.
• Brainstem respiratory control center is divided into the:
  • Inspiratory center: Efferent nerves stimulate spontaneous and rhythmic contraction of the diaphragm (phrenic nerves) and intercostal muscles.
    • The apneustic center, located in the pons, provides a constant stimulus to the inspiratory center and is inhibited by the pneumotaxic center.
    • The pneumotaxic center, also located in the pons, provides inhibitor impulses that limit phrenic nerve contraction and overdistension. It antagonizes the apneustic center (constant stimulus) and decreases tidal volume; the absence of the pneumotaxic center would result in increased tidal volume and decreased RR.
    • The Hering–Breuer reflex consists of afferent receptors located in the bronchi and bronchioles that are activated by stretching and non-stretching. Efferent impulses are transmitted via the vagus nerve to the respiratory center. Thus, inflation acts to inhibit inhalation and prevent further inflation. As the expiratory phase begins, the receptors are no longer stretched, impulses are no longer sent, and inhalation can begin again.
  • Expiratory center: Under normal, resting conditions, expiration is a passive process via relaxation of the diaphragm and intercostals as well as elastic recoil of the lungs; there is no activity within the expiratory center. With "fight or flight," the center stimulates forceful expiration by contraction of the abdominal and internal intercostals.
• Afferent input to the respiratory center.
  • Chemoreceptors: Function to maintain carbon dioxide, pH, and oxygen homeostasis by adjusting the rate, depth, and rhythm of respiration. Central chemoreceptors are cells located in the ventrolateral medulla (surface of the fourth ventricle) that are sensitive to the pH of the cerebrospinal fluid (CSF); they provide feedback to the medullary respiratory center. An acidic CSF stimulates increases in MV, whereas an alkalotic CSF inhibits the inspiratory center. Peripheral chemoreceptor cells are located in the carotid bodies and aortic arch and respond to O₂ and CO₂ concentrations in the arterial blood; they transmit information via the glossopharyngeal nerve (IX) and the vagus nerve (X), respectively, to the respiratory center; their feedback regulates the MV on a breath by breath basis.
  • Baroreceptors: The most important groups are situated in the carotid sinus and aortic arch. An increase in arterial blood pressure can cause reflex hypoventilation or apnea. Conversely, hypotension elicits a sympathetic baroreceptor reflex.
  • Proprioceptors are located in muscles, tendons, and joints that sense movement. During "fight or flight," these receptors transmit signals to the respiratory center that increase the RR and tidal volume.
  • Cerebral cortex: Voluntary control can be exerted to take deep, slow breaths.
  • Temperature: In hypothermic states, MV decreases via:
    • Impairment of synaptic transmission.
    • Decreased velocity of neuronal conduction; the ventral surface of the medulla is particularly prone.
    • Respiratory muscles and motor neurons do not appear to be affected by hypothermia.
• Ventilation: The relationship between ventilation and PaCO₂ is described as follows: PaCO₂ = (k) (VCO₂)/V_A, where k is a constant that corrects for the units (k = 0.863), VCO₂ is the metabolic production of carbon dioxide, and V_A is alveolar ventilation. To maintain homeostasis, increases or decreases in the PaCO₂ are met by respective increases or decreases in V_A.
• Composition of the MV is equal to the sum of alveolar ventilation and dead space ventilation.
  • Alveolar ventilation (V_A): The volume of inspired gases reaching the alveoli and taking part in gas exchange in one minute.
  • Dead space (V_D): The volume of inspired gas that does not participate in gas exchange. It comprises gases in non-respiratory airways (conducting airways also known as anatomic dead space) and alveoli that are not perfused (alveolar dead space).

Pregnancy Considerations

Pediatric Considerations

Pediatric Considerations

• Alveolar hypoventilation: Normal and continued removal of CO₂ from the blood is dependent on adequate MV. In the event that V_A is affected, or does not adequately complement changes in PaCO₂, a respiratory acidosis or alkalosis may result.
• Obesity hypoventilation syndrome (OHS) or Pickwickian syndrome: Defined as a combination of obesity (BMI >30 kg/m²) and awake arterial hypercapnia (PaCO₂ >45 mm Hg) in the absence of other known causes of hypoventilation. Although the precise mechanism is unknown, it is believed to result from the combination of:
  • Impaired respiratory mechanics reflective of a restrictive ventilatory defect: OHS patients have decreased total lung capacity, vital capacity, functional residual capacity, and compliance as well as increased residual volume, work of breathing, and airway resistance.
  • Abnormal medullary respiratory center control: OHS patients appear to lack a compensatory increased ventilatory drive to offset the effects of the mechanical restrictions of obesity. Conversely, obese patients without OHS appear to have an augmented ventilatory response.
  • Neurohormonal aberrancies: Leptin is normally produced by the adipose tissue and acts on the central respiratory center to stimulate ventilation. In OHS patients, there appears to be a leptin deficiency that results in hypoventilation.
• COPD: Hypoventilation is secondary to multiple mechanisms. Patients usually present with severe airway obstruction as well as a decreased responsiveness to hypoxia and hypercapnia. In advanced stages, or periods of decompensation, tidal volume is decreased, RR is increased, and work of breathing is increased resulting in a rapid shallow respiratory pattern. In addition, diaphragmatic dysfunction may result from muscle fatigue and limited movement, leading to an increased V_D/V_A. In patients with airflow obstruction, inhomogeneities in ventilation are responsible for the increase in dead space.

• General anesthesia.
  • Equipment or apparatus dead space is increased and can be clinically relevant in low MV ventilation states or in pediatrics. To avoid hypercarbia and acidosis, measures to decrease the dead space volume or increase MV need to be adjusted accordingly.
  • Inhaled anesthetics produce dose-dependent and drug-specific effects on the breathing pattern, ventilatory response to CO₂ and hypoxemia, and airway resistance. The net effect is a rapid and shallow pattern of breathing, a net decrease in MV, and increase in the PaCO₂.
    • Tidal volumes are decreased via direct depression of the medullary respiratory center (central effect), as well as impaired intercostal muscle and diaphragm function (peripheral effect).
    • There is reduced activity of the pre-Bötzinger complex situated in the ventrolateral medulla of the brainstem; this area is assumed to be the core of the respiratory rhythm generation (respiratory pacemaker).
    • The GABA agonist effect inhibits both inspiratory and expiratory neurons.
  • Intravenous anesthetics: Propofol, barbiturates, and benzodiazepines, with the exception of ketamine, produce central nervous system depression via their ability to enhance the effects of the inhibitory neurotransmitter GABA and depress the respiratory centers. These agents block mechanoreceptor transmission to the respiratory centers and provoke an apneustic breathing pattern. They also cause a depressant effect on bulbospinal expiratory neurons due to their inhibition of the NMDA receptor.
  • Opioids produce dose-dependent depression of the respiratory rate with compensatory increases in the tidal volume; apnea results at high doses. Effects are primarily through:
    • An antagonist effect on the medullary respiratory center (mediated by the µ opioid receptors) as well as the pre-Bötzinger complex in the ventrolateral medulla.
    • Also affects the Kölliker-Fuse and parabrachial nucleus of the dorsolateral pons (pneumotaxic centre).
• Neuraxial anesthesia: Spinal and epidural anesthesia have very little effect on the pulmonary function (lung volumes, resting MV, dead space, and shunt fraction). In the event of a high block, active inspiratory volumes could be affected by abdominal muscle paralysis. This effect may be more pronounced in patients with pulmonary disease (e.g., COPD) that rely on accessory muscles to maintain the MV. In addition, neuraxial opioids (intrathecal and epidural) can result in immediate or delayed respiratory depression.

• MV = V_T × RR; where MV is minute ventilation, V_T is tidal volume, and RR is respiratory rate.
• PaCO₂ = (k)(VCO₂)/V_A; where PaCO₂ is the partial pressure of carbon dioxide in the arterial blood, k is a constant that corrects for units (k = 0.863), VCO₂ is the metabolic production of carbon dioxide, and V_A is alveolar ventilation.

• Dead Space
• Mechanical Ventilation
• Tidal Volume
• Carotid Body
• Respiratory Acidosis
• Respiratory Alkalosis

Stephane Ledot , MD

Yoram G. Weiss , MD, MBA, FCCM