Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

Background: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O-2 consumption (VO2) indicated a critical limitation of O-2 transport capacity. The Hb concentration quantified at this time point (Hb(crit)) was the primary end-point of the protocol. Secondary endpoints were parameters of hemodynamics, O-2 transport and tissue oxygenation. Results: Hb(crit) was significantly lower in the Roc group (2.4 +/- 0.5 vs. 3.2 +/- 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO2 and total body O-2 extraction rate. As the cardiac index increased simultaneously, total body VO2 only decreased marginally in the Roc group (change of VO2 relative to baseline -1.7 +/- 0.8 vs. 3.2 +/- 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO2. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion). Copyright (C) 2011 S. Karger AG, Base

Human skeletal muscle sympathetic nerve activity, heart rate and limb haemodynamics with reduced blood oxygenation and exercise

Acute systemic hypoxia causes significant increases in human skeletal muscle sympathetic nerve activity (MSNA), heart rate and ventilation. This phenomenon is thought to be primarily mediated by excitation of peripheral chemoreceptors sensing a fall in arterial free oxygen partial pressure (Pa,O2). We directly tested the role of Pa,O2 on MSNA (peroneal microneurography), heart rate, ventilation and leg haemodynamics (n = 7–8) at rest and during rhythmic handgrip exercise by using carbon monoxide (CO) to mimic the effect of systemic hypoxia on arterial oxyhaemoglobin (≈20 % lower O2Hba), while normalising or increasing Pa,O2 (range 40–620 mmHg). The four experimental conditions were: (1) normoxia (Pa,O2≈110 mmHg; carboxyhaemoglobin (COHb) ≈2 %); (2) hypoxia (Pa,O2≈40 mmHg; COHb ≈2 %); (3) CO + normoxia (Pa,O2≈110 mmHg; COHb ≈23 %); and (4) CO + hyperoxia (Pa,O2≈620 mmHg; COHb ≈24 %). Acute hypoxia augmented sympathetic burst frequency, integrated MSNA, heart rate and ventilation compared to normoxia over the entire protocol (7–13 bursts min−1, 100–118 %, 13–17 beats min−1, 2–4 l min−1, respectively, P < 0.05). The major new findings were: (1) CO + normoxia and CO + hyperoxia also elevated MSNA compared to normoxia (63–144 % increase in integrated MSNA; P < 0.05) but they did not increase heart rate (62–67 beats min−1) or ventilation (6.5–6.8 l min−1), and (2) despite the 4-fold elevation in MSNA with hypoxaemia and exercise, resting leg blood flow, vascular conductance and O2 uptake remained unchanged. In conclusion, the present results suggest that increases in MSNA with CO are not mediated by activation of the chemoreflex, whereas hypoxia-induced tachycardia and hyperventilation are mediated by activation of the chemoreflex in response to the decline in Pa,O2. Our findings also suggest that Pa,O2 is not an obligatory signal involved in the enhanced MSNA with reduced blood oxygenation