Spontaneous breathing has beneficial effects on the circulation, since negative intrathoracic pressure enhances venous return and increases cardiac stroke volume. We quantified the contribution of the respiratory pump to preserve stroke volume during hypovolemia in awake, young, healthy subjects. Noninvasive stroke volume, cardiac output, heart rate, and mean arterial pressure (Finometer) were recorded in 31 volunteers (19 women), 19-30 yr old, during normovolemia and hypovolemia (approximating 450- to 500-ml reduction in central blood volume) induced by lower-body negative pressure. Control-mode noninvasive positive-pressure ventilation was employed to reduce the effect of the respiratory pump. The ventilator settings were matched to each subject's spontaneous respiratory pattern. Stroke volume estimates during positive-pressure ventilation and spontaneous breathing were compared with Wilcoxon matched-pairs signed-rank test. Values are overall medians. During normovolemia, positive-pressure ventilation did not affect stroke volume or cardiac output. Hypovolemia resulted in an 18% decrease in stroke volume and a 9% decrease in cardiac output ( P < 0.001). Employing positive-pressure ventilation during hypovolemia decreased stroke volume further by 8% ( P < 0.001). Overall, hypovolemia and positive-pressure ventilation resulted in a reduction of 26% in stroke volume ( P < 0.001) and 13% in cardiac output ( P < 0.001) compared with baseline. Compared with the situation with control-mode positive-pressure ventilation, spontaneous breathing attenuated the reduction in stroke volume induced by moderate hypovolemia by 30% (i.e., -26 vs. -18%). In the patient who is critically ill with hypovolemia or uncontrolled hemorrhage, spontaneous breathing may contribute to hemodynamic stability, whereas controlled positive-pressure ventilation may result in circulatory decompensation. NEW & NOTEWORTHY Maintaining spontaneous respiration has beneficial effects on hemodynamic compensation, which is clinically relevant for patients in intensive care. We have quantified the contribution of the respiratory pump to cardiac stroke volume and cardiac output in healthy volunteers during normovolemia and central hypovolemia. The positive hemodynamic effect of the respiratory pump was abolished by noninvasive, low-level positive-pressure ventilation. Compared with control-mode positive-pressure ventilation, spontaneous negative-pressure ventilation attenuated the fall in stroke volume by 30%.

Intact cerebral blood flow (CBF) is essential for cerebral metabolism and function, whereas hypoperfusion in relation to hypovolemia and hypocapnia can lead to severe cerebral damage. This study was designed to assess internal carotid artery blood flow (ICA‐BF) during simulated hypovolemia and noninvasive positive pressure ventilation (PPV) in young healthy humans. Beat‐by‐beat blood velocity (ICA and aorta) were measured by Doppler ultrasound during normovolemia and simulated hypovolemia (lower body negative pressure), with or without PPV in 15 awake subjects. Heart rate, plethysmographic finger arterial pressure, respiratory frequency, and end‐tidal CO 2 (ETCO 2) were also recorded. Cardiac index (CI) and ICA‐BF were calculated beat‐by‐beat. Medians and 95% confidence intervals and Wilcoxon signed rank test for paired samples were used to test the difference between conditions. Effects on ICA‐BF were modeled by linear mixed‐effects regression analysis. During spontaneous breathing, ICA‐BF was reduced from normovolemia (247, 202–284 mL/min) to hypovolemia (218, 194–271 mL/min). During combined PPV and hypovolemia, ICA‐BF decreased by 15% (200, 152–231 mL/min, P = 0.001). Regression analysis attributed this fall to concurrent reductions in CI (β: 43.2, SE: 17.1, P = 0.013) and ETCO 2 (β: 32.8, SE: 9.3, P = 0.001). Mean arterial pressure was maintained and did not contribute to ICA‐BF variance. In healthy awake subjects, ICA‐BF was significantly reduced during simulated hypovolemia combined with noninvasive PPV. Reductions in CI and ETCO 2 had additive effects on ICA‐BF reduction. In hypovolemic patients, even low‐pressure noninvasive ventilation may cause clinically relevant reductions in CBF, despite maintained arterial blood pressure.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Little is known about how implementation of pneumoperitoneum and head-up tilt position contributes to general anesthesia-induced decrease in cerebral blood flow in humans. We investigated this question in patients undergoing laparoscopic cholecystectomy, hypothesizing that cardiorespiratory changes during this procedure would reduce cerebral perfusion. Methods In a nonrandomized, observational study of 16 patients (American Society of Anesthesiologists physical status I or II) undergoing laparoscopic cholecystectomy, internal carotid artery blood velocity was measured by Doppler ultrasound at four time points: awake, after anesthesia induction, after induction of pneumoperitoneum, and after head-up tilt. Vessel diameter was obtained each time, and internal carotid artery blood flow, the main outcome variable, was calculated. The authors recorded pulse contour estimated mean arterial blood pressure (MAP), heart rate (HR), stroke volume (SV) index, cardiac index, end-tidal carbon dioxide (ETco2), bispectral index, and ventilator settings. Results are medians (95% CI). Results Internal carotid artery blood flow decreased upon anesthesia induction from 350 ml/min (273 to 410) to 213 ml/min (175 to 249; −37%, P &lt; 0.001), and tended to decrease further with pneumoperitoneum (178 ml/min [127 to 208], −15%, P = 0.026). Tilt induced no further change (171 ml/min [134 to 205]). ETco2 and bispectral index were unchanged after induction. MAP decreased with anesthesia, from 102 (91 to 108) to 72 (65 to 76) mmHg, and then remained unchanged (Pneumoperitoneum: 70 [63 to 75]; Tilt: 74 [66 to 78]). Cardiac index decreased with anesthesia and with pneumoperitoneum (overall from 3.2 [2.7 to 3.5] to 2.3 [1.9 to 2.5] l · min−1 · m−2); tilt induced no further change (2.1 [1.8 to 2.3]). Multiple regression analysis attributed the fall in internal carotid artery blood flow to reduced cardiac index (both HR and SV index contributing) and MAP (P &lt; 0.001). Vessel diameter also declined (P &lt; 0.01). Conclusions During laparoscopic cholecystectomy, internal carotid artery blood flow declined with anesthesia and with pneumoperitoneum, in close association with reductions in cardiac index and MAP. Head-up tilt caused no further reduction. Cardiac output independently affects human cerebral blood flow.

Controlling respiration in awake healthy humans reduced HR variability and increased CBF variability in hypovolemia and normovolemia. We suggest respiration-induced HR variability to be a mechanism in CBF regulation. Maintaining spontaneous respiration in patients receiving ventilatory support may be beneficial also for cerebral circulatory purposes.