Perflubron emulsion delays blood transfusions in orthopedic surgery. European Perflubron Emulsion Study Group.
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BACKGROUND: Fluorocarbon emulsions have been proposed as temporary artificial oxygen carriers. The aim of the present study is to compare the effectiveness of perflubron emulsion with the effectiveness of autologous blood or colloid infusion for reversal of physiologic transfusion triggers. METHODS: A multinational, multicenter, randomized, controlled, single-blind, parallel group study was performed in 147 orthopedic patients. Patients underwent acute normovolemic hemodilution with colloid to a target hemoglobin of 9 g/dl with an inspiratory oxygen fraction (FIO2) of 0.40. Patients were then randomized into one of four treatment groups after having reached any of the protocol-defined transfusion triggers including tachycardia (heart rate > 125% of posthemodilution rate or > 110 bpm), hypotension (mean arterial pressure < 75% of posthemodilution level or < or = 60 mmHg), elevated cardiac output (> 150% of posthemodilution level) or decreased mixed venous oxygen partial pressure (PVO2; < 38 mmHg). Treatments in the four groups were 450 ml autologous blood harvested during acute normovolemic hemodilution given at FO2 = 0.40; 450 ml colloid at FIO2 = 1.0; 0.9 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0; and 1.8 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0. The primary endpoint was duration of transfusion-trigger reversal. A secondary end-point was percentage of transfusion-trigger reversal. RESULTS: Perflubron emulsion was well tolerated with no serious adverse event attributed to drug treatment. Duration of reversal was longest in the 1.8 g/kg perflubron group (median, 80 min; 95% confidence interval, 60-100 min; P = 0.014 vs. autologous blood, P < 0.001 vs. colloid) followed by the 0.9 g/kg perflubron group (median, 59 min; 95% confidence interval, 40-90 min), the autologous blood group (median, 55 min; 95% confidence interval, 30-70 min) and the colloid group (median, 30 min; 95% confidence interval, 27-60 min). Percentage of reversal was also highest in the 1.8 g/kg perflubron group (97%; P < 0.001 vs. autologous blood; P = 0.014 vs. colloid), followed by 0.9 g/kg perflubron (82%), colloid (76%), and autologous blood (60%). CONCLUSIONS: Perflubron emulsion (1.8 g/kg) combined with 100% oxygen ventilation is more effective than autologous blood or colloid infusion in reversing physiologic transfusion triggers. (+info)
Modifications of blood volume alter the disposition of markers of blood volume, extracellular fluid, and total body water.
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Recirculatory pharmacokinetic models for indocyanine green (ICG), inulin, and antipyrine describe intravascular mixing and tissue distribution after i.v. administration. These models characterized physiologic marker disposition in four awake, splenectomized dogs while they were normovolemic, volume loaded (15% of estimated blood volume added as a starch solution), and mildly and moderately hypovolemic (15 and 30% of estimated blood volume removed). ICG-determined blood volumes increased 20% during volume loading and decreased 9 and 22% during mild and moderate hypovolemia. Dye (ICG) dilution cardiac output (CO) increased 31% during volume loading and decreased 27 and 38% during mild and moderate hypovolemia. ICG-defined central and fast peripheral intravascular circuits accommodated blood volume alterations and the fast peripheral circuit accommodated blood flow changes. Inulin-defined extracellular fluid volume contracted 14 and 21% during hypovolemia. Early inulin disposition changes reflected those of ICG. The ICG and inulin elimination clearances were unaffected by altered blood volume. Neither antipyrine-defined total body water volume nor antipyrine elimination clearance changed with altered blood volume. The fraction of CO not involved in drug distribution had a significant effect on the area under the antipyrine concentration-versus-time relationships (AUC) in the first minutes after drug administration. Hypovolemia increased the fraction of CO represented by nondistributive blood flow and increased the antipyrine AUC up to 60% because nondistributive blood flow did not change, despite decreased CO. Volume loading resulted in a smaller (less than 20%) antipyrine AUC decrease despite increased fast tissue distributive flow because nondistributive flow also increased with increased CO. (+info)
Hemodynamic patterns and spectral analysis of heart rate variability during dialysis hypotension.
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Intradialytic hypotension, a major source of morbidity during hemodialysis and ultrafiltration, is often accompanied by paradoxical bradycardia. Relatively little is known about the sequential changes in autonomic nervous system activity up to and during the hypotensive episode. Continuous, beat-to-beat measurements of BP and heart rate were made during hemodialysis in patients prone (n = 8) and not prone (n = 11) to develop intradialytic hypotension. Off-line spectral analysis of heart rate variability (HRV) was performed to assess changes in autonomic nervous system activity during dialysis sessions both with and without hypotension. The low frequency (LF) component of HRV is thought to correlate with sympathetic nervous system activity, the high frequency (HF) component with that of the parasympathetic nervous system. In the sessions not complicated by symptomatic hypotension (n = 26), mean arterial BP (MAP) hardly fell, whereas heart rate increased from 77 +/- 2 to 89 +/- 5 bpm (P < 0.05). The LF component of HRV increased from 45.2 +/- 5.0 normalized units (nu) to 59.9 +/- 4.9 nu (P < 0.05), whereas the HF component fell from 54.8 +/- 5.0 to 40.2 +/- 4.4 nu (P < 0.05). These changes agree with compensatory baroreflex-mediated activation of the sympathetic nervous system (and suppressed parasympathetic activity) during ultrafiltration-induced intravascular volume depletion. In the sessions complicated by severe symptomatic hypotension (n = 22), the changes in heart rate and the results of spectral analysis of HRV were similar to those reported above up to the moment of sudden symptomatic (nausea, vomiting, dizziness, cramps) hypotension, whereas MAP had already fallen gradually from 94 +/- 3 to 85 +/- 3 mmHg (P < 0.05). The sudden further reduction in MAP (to 55 +/- 2 mmHg, P < 0.02) was invariably accompanied by bradycardia (heart rate directly before hypotension 90 +/- 2 bpm, during hypotension 69 +/- 3 bpm, P < 0.002). The LF component of HRV fell from 62.8 +/- 4.6 nu directly before to 40.0 +/- 3.7 nu (P < 0.05) during hypotension, whereas the HF component increased from 37.9 +/- 4.7 to 60.3 +/- 3.7 nu (P < 0.05). These findings agree with activation of the cardiodepressor reflex, involving decreased sympathetic and increased parasympathetic nervous system activity, respectively. These findings indicate that activation of the sympatho-inhibitory cardiodepressor reflex (Bezold-Jarisch reflex), which is a physiologic response to a critical reduction in intravascular volume and cardiac filling, is the cause of sudden intradialytic hypotension. (+info)
Cardiovascular response to acute hypovolemia in relation to age. Implications for orthostasis and hemorrhage.
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Venous compliance in the legs of aging man has been found to be reduced with decreased blood pooling (capacitance response) in dependent regions, and this might lead to misinterpretations of age-related changes in baroreceptor function during orthostasis. The hemodynamic response to hypovolemic circulatory stress was studied with the aid of lower-body negative pressure (LBNP) of 60 cmH(2)O in 33 healthy men [18 young (mean age 22 yr) and 15 old (mean age 65 yr)]. Volumetric technique was used in the study of capacitance responses in the calf and arm as well as transcapillary fluid absorption in the arm. LBNP led to smaller increase in heart rate (P < 0.001) and peripheral resistance (P < 0.01) and reduced transcapillary fluid absorption in the arm (P < 0.05) in old subjects. However, blood pooling in the calf was reduced in old subjects (1.66 +/- 0.10 vs. 2.17 +/- 0.13 ml/100 ml tissue; P < 0. 01). Accordingly, during similar blood pooling in the calf (LBNP 80 cmH(2)O in old subjects), no changes in cardiovascular reflex responses with age were found. The capacitance response in the arm (mobilization of peripheral blood to the central circulation) was still reduced, however (0.67 +/- 0.10 vs. 1.37 +/- 0.11 ml/100 ml tissue; P < 0.01). Thus the reduced cardiovascular reflex response found in the elderly during orthostatic stress seems to be caused by a reduced capacitance response in the legs with age and a concomitant smaller central hypovolemic stimulus rather than a reduced efficiency of the reflex response. With similar hypovolemic circulatory stress, no changes in cardiovascular reflex responses are seen with age. The capacitance response in the arm (mobilization of peripheral blood toward the central circulation) is reduced, however, by approximately 50% in the elderly. This might seriously impede the possibility of survival of an acute blood loss. (+info)
Postoperative hypertensive-hypervolaemic-haemodilution (Triple H) therapy in the treatment of vasospasm following aneurysmal subarachnoid haemorrhage.
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Twenty five patients with post operative ischaemic deficits, following clipping of intracranial aneurysms, were studied. Hypertensive-hypervolaemic-haemodilution (triple H) therapy was given to all patients using colloids and crystalloids. CVP was used to monitor the fluid therapy. Dopamine was needed in 22 patients to elevate the systemic blood pressure. Vasospasm was confirmed in 20 patients with transcranial doppler studies (TCD). 20 (80%) patients survived, 10 (40%) with good outcome, 7 (28%) with fair, 2 (8%) with poor outcome and 1 (4%) with vegetative state. There were 5 (20%) deaths, 4 of which occurred due to infarct. All these patients had poor Hunt and Hess grade at admission, high Fisher grade haemorrhages in the initial CT scan and/or required prolonged temporary clipping at surgery. One death occurred due to central venous line induced septicaemia. The duration of 'triple H therapy' amongst the survivors varied from 2-7 days with an average of 4.6 days. The complications of 'triple H therapy' included hypokalaemia (3 patients), haemorrhagic infarct (1 patient) and septicaemia (1 patient). It is concluded that 'triple H therapy' is useful in treating vasospasm induced ischaemic deficits. It worsens brain oedema in presence of acute infarcts and hence is contraindicated in such patients. A further study involving a larger number of patients with strict haemodynamic and ICP monitoring is suggested to determine the usefulness of individual components of 'triple H therapy'. (+info)
Influence of hypovolemia on the pharmacokinetics and the electroencephalographic effect of propofol in the rat.
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BACKGROUND: Hypovolemia decreases the dose requirement for anesthetics, but no data are available for propofol. As it is impossible to study this in patients, a rat model was used in which the influence of hypovolemia on the pharmacokinetics and pharmacodynamics of propofol was investigated. METHODS: Animals were randomly allocated to either a control (n = 9) or a hypovolemia (n = 9) group, and propofol was infused (150 mg x kg(-1) x h(-1)) until isoelectric periods of 5 s or longer were observed in the electroencephalogram. The changes observed in the electroencephalogram were quantified using aperiodic analysis and used as a surrogate measure of hypnosis. The righting reflex served as a clinical measure of hypnosis. RESULTS: The propofol dose needed to reach the electroencephalographic end point in the hypovolemic rats was reduced by 60% (P < 0.01). This could be attributed to a decrease in propofol clearance and in distribution volume. Protein binding was similar in both groups. To investigate changes in end organ sensitivity during hypovolemia, the electroencephalographic effect versus effect-site concentration relation was studied. The effect-blood concentration relation was biphasic, exhibiting profound hysteresis in both hypovolemic and control animals. Semiparametric minimization of this hysteresis revealed similar equilibration half-lives in both groups. The biphasic effect-concentration relation was characterized by descriptors showing an increased potency of propofol during hemorrhage. The effect-site concentration at the return of righting reflex was 23% (P < 0.01) lower in the hypovolemic animals, also suggesting an increased end organ sensitivity. CONCLUSIONS: An increased hypnotic effect of propofol occurs during hypovolemia in the rat and can be attributed to changes in both pharmacokinetics and end organ sensitivity. (+info)
Issues in contemporary fluid management.
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Fluid management strategies need to be guided by an understanding of the pathophysiologic mechanisms underlying fluid imbalance. In the hypovolaemic patient, reduced circulating blood volume and venous return and, in severe cases, altered tissue perfusion may initiate a cascade of pathophysiologic processes culminating in multiple organ failure. The objectives of fluid management are to maintain adequate blood pressure, tissue oxygenation and intravascular fluid volume. Both crystalloids and colloids can be useful for these purposes. In the hypovolaemic patient with normal pulmonary function, the use of colloids to maintain colloid osmotic pressure can limit the development of peripheral as well as pulmonary oedema. However, choice of fluid is less important in states of increased lung capillary permeability. Further evidence is needed to broaden understanding of the optimal roles for particular fluid management strategies. Experimental models can make an important contribution in gathering such evidence. Rigorous pharmacoeconomic studies are also needed to define the benefits and costs of differing fluid regimens. (+info)
Pathophysiology of fluid imbalance.
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Fluid imbalance can arise due to hypovolemia, normovolemia with maldistribution of fluid, and hypervolemia. Trauma is among the most frequent causes of hypovolemia, with its often profuse attendant blood loss. Another common cause is dehydration, which primarily entails loss of plasma rather than whole blood. The consequences of hypovolemia include reduction in circulating blood volume, lower venous return and, in profound cases, arterial hypotension. Myocardial failure may result from increased myocardial oxygen demand in conjunction with reduced tissue perfusion. Finally, anaerobic metabolism due to reduced perfusion may produce acidosis and, together with myocardial dysfunction, precipitate multi-organ failure. The splanchnic organs are particularly susceptible to the deleterious effects of hypotension and hypovolemic shock, and these effects, depending upon their duration and severity, may be irreversible despite restoration of normovolemia by fluid administration. Patient monitoring in the intensive care unit typically relies upon central venous pressure devices, whereas the primary focus in the operating theater is blood volume deficit estimated from suction devices. However, estimates of intraoperative blood loss can be inaccurate, potentially leading to inappropriate fluid management. Normovolemia with maldistribution of fluid can be encountered in shock-specific microcirculatory disorders secondary to hypovolemia, as well as pain and stress. Consequent vasoconstriction and reduced tissue driving pressure, as well as leukocyte and platelet adhesion, and liberation of humoral and cellular mediators, may impair or abolish blood flow in certain areas. The localized perfusion deficit may contribute to multi-organ failure. Choice of resuscitation fluid may be important in this context, since some evidence suggests that at least certain colloids might be helpful in diminishing post-ischemic microvascular leukocyte adherence. Excessive volume administration may lead to fluid overload and associated impairment of pulmonary function. However, entry of fluid into the lungs may also be facilitated by increased vascular permeability in certain pathologic conditions, especially sepsis and endotoxemia, even in the absence of substantially rising hydrostatic pressure. Another condition associated with elevated vascular permeability is systemic capillary leak syndrome. The chief goal of fluid management, based upon current understanding of the pathophysiology of fluid imbalance, should be to ensure adequate oxygen delivery by optimizing blood oxygenation, perfusion pressure, and circulating volume. (+info)