Anesthesia and analgesia
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Anesthesia and analgesia · Oct 1998
Uncompensated blood loss is not tolerated during acute normovolemic hemodilution in anesthetized pigs.
Clinically, hemodilution to a hematocrit of 9% has been studied, but the effects of hypovolemia during this degree of hemodilution have not been elucidated. We studied the response to blood loss during extreme hemodilution and evaluated indicators of hypovolemia. Systemic and myocardial hemodynamics, oxygen transport, and blood lactate concentrations were measured in 12 anesthetized pigs exposed to a graded blood loss of 10, 20, 30, and 40 mL/kg. Six animals were hemodiluted (hematocrit 10.8% +/- 1.4%, mean +/- SD), and six animals served as controls (hematocrit 34.6% +/- 1.5%). Hemodilution decreased systemic oxygen delivery to 9.5 +/- 0.6 mL x kg(-1) x min(-1) (controls 21.7 +/- 3.9 mL x kg(-1) x min(-1)) (P < 0.01) despite a 31% increase in cardiac output. Systemic oxygen uptake was unchanged. Arterial lactate increased to 3.3 +/- 1.1 mM/L (controls 1.6 +/- 0.6 mM/L) (P < 0.05), and mixed venous oxygen saturation (SvO2) decreased to 38.2% + 4.8% (controls 68.6% +/- 2.9%) (P < 0.01). At a blood loss of 10 mL/kg, cardiac output continued to be greater in the hemodiluted animals (P < 0.01). Arterial blood pressure decreased to 61 +/- 8 mmHg (controls 84 +/- 18 mm Hg) (P < 0.05), whereas heart rate was unchanged. Systemic oxygen delivery decreased to 8.8 +/- 1.2 mL x kg(-1) x min(-1) (controls 14.1 +/- 2.5 mL x kg(-1) x min(-1)) (P < 0.01). Systemic oxygen uptake was maintained by a further increase in oxygen extraction, and SvO2 decreased to 29.7% +/- 7.3%, compared with 55.3% +/- 9.0% in controls (P < 0.01). Arterial lactate increased to 4.9 +/- 1.4 mM/L (controls 1.8 +/- 0.8 mM/L) (P < 0.01). Myocardial oxygen delivery and lactate uptake were unchanged. When the blood loss equaled 30 mL/kg, myocardial lactate production occurred, and two hemodiluted animals died of circulatory failure. Central venous and capillary wedge pressures changed minimally during the blood loss and did not differ between groups. We conclude that a decrease in arterial blood pressure and SvO2 were early signs of hypovolemia during hemodilution, whereas central venous pressure and pulmonary capillary wedge pressure were insensitive indicators. ⋯ Anesthetized pigs with extremely low hemoglobin levels (one third of normal) showed poor tolerance to blood loss >10 mL/kg. A decreasing arterial blood pressure, a decreasing oxygen saturation in the venous blood, and an increase in arterial blood lactate concentration were useful indicators of blood loss.
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Anesthesia and analgesia · Oct 1998
Protamine reversal of heparin affects platelet aggregation and activated clotting time after cardiopulmonary bypass.
Bleeding after cardiopulmonary bypass (CPB) is related to multiple factors. Excess protamine weakens clot structure and decreases platelet function; therefore, an increased activated clotting time (ACT) after protamine reversal of heparin may be misinterpreted as residual heparin anticoagulation. We evaluated the effects of protamine, recombinant platelet factor 4 (rPF4), and hexadimethrine on ACT in blood obtained after CPB. In addition, we examined the effect of protamine on in vitro platelet aggregation. Incremental doses of protamine, rPF4, and hexadimethrine were added to heparinized blood from CPB, and ACTs were performed. Incremental concentrations of protamine were added to heparinized platelet-rich plasma, and aggregometry was induced by adenosine diphosphate (ADP) and collagen. The mean heparin concentration at the end of CPB was 3.3 U/mL. Protamine to heparin ratios >1.3:1 produced a significant prolongation of the ACT that was not seen with rPF4 and was observed only with 5:1 hexadimethrine to heparin ratios. ADP-induced platelet aggregation was reduced with protamine administration > or =1.3:1. Excessive protamine reversal of heparin prolongs ACT and alters ADP-induced platelet aggregation in a dose-dependent manner in vitro. Additional protamine administered to treat a prolonged ACT may further increase clotting time, reduce platelet aggregation, and potentially contribute to excess bleeding after CPB. ⋯ We found that excess protamine prolonged the activated clotting time and altered platelet function after cardiopulmonary bypass, whereas heparin antagonists, such as recombinant platelet factor 4 and hexadimethrine, exhibited a wider therapeutic range without adversely affecting the activated clotting time. Approaches to avoid excess protamine or use of alternative heparin antagonists after cardiopulmonary bypass may be beneficial.
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Anesthesia and analgesia · Oct 1998
Reliability of the transient hyperemic response test in detecting changes in cerebral autoregulation induced by the graded variations in end-tidal carbon dioxide.
The transient hyperemic response (THR) in the middle cerebral artery (MCA) after the release of brief compression of the ipsilateral common carotid artery has been used to study cerebral autoregulation. We conducted the present study to evaluate the reliability of THR to detect changes in cerebral autoregulation induced by graded variations in PETCO2. Seven healthy adult volunteers were recruited. Fifteen THR tests were performed on every volunteer: three at baseline PETCO2, three each at PETCO2 of 7.5 mm Hg and 15 mm Hg above the baseline, and then three each at PETCO2 of 7.5 mm Hg and 15 mm Hg below the baseline. Transient hyperemic response ratio (THRR) and strength of autoregulation (SA) were calculated using established formulae. Both THRR and SA were highly sensitive (96%) in detecting the changes in cerebral autoregulation induced by graded changes in PETCO2. The within-individual variability of SA was significantly smaller than that of THRR at all levels of PETCO2. ⋯ This study demonstrates the reliability of the THR test, when used for repetitive measurements, in detecting changes in cerebral autoregulation induced by graded changes in PETCO2. This test may provide a simple and noninvasive method of evaluating changes in cerebral autoregulation within an individual.
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Anesthesia and analgesia · Oct 1998
The effect of hyperventilation and hyperoxia on cerebral venous oxygen saturation in patients with traumatic brain injury.
Eighteen head-injured patients undergoing hyperventilation were studied for changes in jugular venous oxygen saturation (SjvO2) and arteriovenous oxygen content difference (AVDO2) in response to changes in PaO2 and PaCO2. SjvO2 decreased significantly from 66% +/- 3% to 56% +/- 3% (mean +/- SD) when PaCO2 decreased from 30 to 25 mm Hg at a PaO2 of 100-150 mm Hg. SjvO2 values returned to baseline (66% +/- 2%) when PaCO2 was restored to 30 mm Hg. Repetition of the study at a PaO2 of 200-250 mm Hg produced a similar pattern. However, SjvO2 values were significantly greater with PaO2 within the range of 200-250 mm Hg (77% +/- 4% and 64% +/- 3%) than SjvO2 measured at a PaO2 of 100-150 mm Hg at PaCO2 values of both 30 and 25 mm Hg. AVDO2 also improved with a PaO2 of 200-250 mm Hg at each PaCO2 (P < 0.001). In conclusion, decreases in SjvO2 associated with decreases in PaCO2 may be offset by increasing PaO2. ⋯ The adequacy of cerebral oxygenation can be estimated in head-injured patients by monitoring jugular bulb oxygen saturation and the arteriovenous oxygenation content difference. Increasing the partial pressure of arterial oxygen above normal offset deleterious effects of hyperventilation on jugular bulb oxygen saturation and arteriovenous oxygenation content difference in head-injured patients.
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Anesthesia and analgesia · Oct 1998
Fundamental properties of local anesthetics: half-maximal blocking concentrations for tonic block of Na+ and K+ channels in peripheral nerve.
Local anesthetics suppress excitability by interfering with ion channel function. Ensheathment of peripheral nerve fibers, however, impedes diffusion of drugs to the ion channels and may influence the evaluation of local anesthetic potencies. Investigating ion channels in excised membrane patches avoids these diffusion barriers. We investigated the effect of local anesthetics with voltage-dependent Na+ and K+ channels in enzymatically dissociated sciatic nerve fibers of Xenopus laevis using the patch clamp method. The outside-out configuration was chosen to apply drugs to the external face of the membrane. Local anesthetics reversibly blocked the transient Na+ inward current, as well as the steady-state K+ outward current. Half-maximal tonic inhibiting concentrations (IC50), as obtained from concentration-effect curves for Na+ current block were: tetracaine 0.7 microM, etidocaine 18 microM, bupivacaine 27 microM, procaine 60 microM, mepivacaine 149 microM, and lidocaine 204 microM. The values for voltage-dependent K+ current block were: bupivacaine 92 microM, etidocaine 176 microM, tetracaine 946 microM, lidocaine 1118 microM, mepivacaine 2305 microM, and procaine 6302 microM. Correlation of potencies with octanol:buffer partition coefficients (logP0) revealed that ester-bound local anesthetics were more potent in blocking Na+ channels than amide drugs. Within these groups, lipophilicity governed local anesthetic potency. We conclude that local anesthetic action on peripheral nerve ion channels is mediated via lipophilic drug-channel interactions. ⋯ Half-maximal blocking concentrations of commonly used local anesthetics for Na+ and K+ channel block were determined on small membrane patches of peripheral nerve fibers. Because drugs can directly diffuse to the ion channel in this model, these data result from direct interactions of the drugs with ion channels.