Apnea and deteriorating ventilation despite other therapeutic measures are absolute indications for mechanical breathing assistance. Usually in such cases there are signs of respiratory distress or advancing obtundation, and serial blood gas measurements show a falling pH and stable or rising PaCO₂. Although few physicians withhold mechanical assistance when the pH trends steadily downward and there are signs of physiologic intolerance, there is less agreement regarding the absolute values of PaCO₂ and pH that warrant such intervention; these clearly vary with the specific clinical setting. In fact, after intubation has been accomplished, pH and PaCO₂ may be allowed to drift deliberately far outside the normal range to avoid the high ventilating pressures and tidal volumes that tend to induce lung damage. This strategy—permissive hypercapnia—is now considered integral to a lungprotective ventilatory approach for the acute management of severe asthma and adult acute respiratory distress syndrome (ARDS). Acute hypercapnia has well-known and potentially adverse physiologic consequences. Nonetheless, recent experimental work in varied models of clinical problems—notably, ischemia/reperfusion and ventilator-induced lung injury—clearly indicate that certain forms of cellular injury are actually attenuated by hypercapnia. Whether it is hypercapnia itself or the associated change in hydrogen ion concentration is still a subject of active investigation (ARDS; see Chapter 24).

Blood pH is generally a better indicator than PaCO₂ of the need for ventilatory support. Hypercapnia per se should not prompt aggressive intervention if pH remains acceptable and the patient remains alert, especially if CO₂ retention occurs slowly. Many patients require ventilatory assistance despite levels of alveolar ventilation that would be appropriate for normal resting metabolism. For example, patients with metabolic acidosis and neuromuscular weakness or airflow obstruction may lower PaCO₂ to 40 mm Hg or below but not sufficiently to prevent acidemia. The physiologic consequences of altered pH are still debated and clearly depend on the underlying pathophysiology and comorbidities. However, if not quickly reversible by simpler measures, a sustained pH greater than 7.65 or less than 7.10 is often considered sufficiently dangerous in itself to require control by mechanical ventilation and sedation (with muscle relaxants, if needed). Inside these extremes, the threshold for initiating support varies with the clinical setting. For example, a lethargic patient with asthma who is struggling to breathe can maintain a normal pH until shortly before suffering a respiratory arrest, whereas an alert cooperative patient with chronically blunted respiratory drive may allow pH to fall to 7.25 or lower before recovering uneventfully in response to aggressive
bronchodilation, steroids, and oxygen. In less obvious situations, the decision to ventilate should be guided by trends in pH, arterial blood gases, mental status, dyspnea, hemodynamic stability, and response to therapy. The ongoing need for ventilatory assistance must be carefully and repeatedly assessed (see Chapter 10).

A common reason for mechanical assistance is a lack of ventilatory power or reserve. The respiratory muscles cannot sustain tidal pressures greater than 40% to 50% of their maximal isometric pressure. Respiratory pressure requirements rise with minute ventilation and the impedance to breathing. Patients with hypermetabolism or metabolic acidosis often need ventilatory support to avoid decompensation. Impaired ventilatory drive or muscle strength diminish ventilatory capacity and reserve.

Although little effort is expended by normal subjects who breathe quietly, the O₂ demands of the respiratory system account for a very high percentage of total body oxygen consumption ([V with dot above]O₂) during periods of physiologic stress (Fig. 7-2). Experimental animals in circulatory shock who receive mechanical ventilation survive longer than their unassisted counterparts. Moreover, patients with combined cardiorespiratory disease often fail attempts to withdraw ventilatory support for cardiac rather than respiratory reasons. Such observations demonstrate the importance of minimizing the ventilatory O₂ requirement during cardiac insufficiency or ischemia. Doing so helps rebalance myocardial O₂ supply with requirements and/or allows diaphragmatic blood flow to be redirected to other O₂-deprived vital organs. Moreover, reducing ventilatory effort may improve afterload to the left ventricle (see Chapter 1). Therefore, the physician should intervene early to relieve an excessive breathing workload for patients with compromised cardiac function. Although it is possible to use NIV or CPAP alone for mildly to moderately affected patients, fatigue often sets in unless underlying oxygen requirements are reduced substantially, which often requires adequate sedation or higher pressures than can be provided noninvasively.