Evaluation of genotoxicity of general anesthesia maintained with desflurane in patients under minor surgery.

There is controversy over the genotoxic effects of volatile anesthetics. The available literature on the genotoxicity of desflurane, one of the newest volatile halogenated agents used for general anesthesia maintenance, is scarce. This study aimed to evaluate the genotoxic potential of desflurane in 15 patients without comorbidities, of both sexes, who underwent minor surgeries lasting at least 90 min. Patients enrolled in the study received desflurane anesthesia (6%); blood samples were collected before anesthesia induction (T0), 90 min after the beginning of anesthesia (T1), and on the day following surgery (T2). DNA damage was evaluated in lymphocytes using the alkaline comet assay. We found statistically significant increases in DNA damage in T2 samples compared to T0. The findings suggest that desflurane anesthesia induces DNA strand breaks/alkali-labile sites on the day after minimally invasive surgery in healthy patients.

Effects of magnesium sulphate on the pharmacodynamics of rocuronium in patients aged 60 years and older: A randomised trial.

BACKGROUND: There is little information on the interaction between magnesium sulphate (MgSO4) and rocuronium in elderly patients. With a growing number of older patients who need surgical procedures, it is increasingly important to study this age group. OBJECTIVE: To evaluate the effects of MgSO4 administration on the pharmacodynamics of rocuronium in patients aged 60 years or older. DESIGN: A randomised controlled trial. SETTING: A tertiary care hospital. PATIENTS: Sixty-four patients, aged 60 years or older, American Society of Anesthesiologists (ASA) physical status classes I to III, scheduled for elective oncological head and neck surgery. Exclusion criteria were severe renal insufficiency (calculated creatinine clearance <30 ml min(-1)), preoperatorive serum magnesium concentration of more than 1.25 mmol l(-1) and patients receiving drugs known to affect neuromuscular function. INTERVENTIONS: Patients were randomly allocated to one of two groups: in the magnesium group, patients received MgSO4 30 mg kg(-1) intravenously, for 10 min, and then a continuous intravenous infusion at a rate of 1 g h(-1). The control group received the same volume of physiological saline. Neuromuscular function was evaluated continuously in both groups. MAIN OUTCOME MEASURES: Total recovery time was the primary outcome. Onset time, clinical duration, recovery index and recovery time were considered as secondary endpoints. Values are given as mean [SD]. RESULTS: Total recovery time from neuromuscular block (NMB) was 113 [36] min in the magnesium group and 101 [39] min in the control group. Clinical duration was 69 [23] min in the magnesium group and 59 [28] min in the control group. Recovery index was 19 [36] min in the magnesium group and 17 [6] min in the control group. Recovery time was 44 [22] min in the magnesium group and 42 [18] min in the control group. There were no statistically significant differences between the groups in any of the recovery indices. In the magnesium group, the mean onset time was 144 [58] s, significantly shorter than the onset time in the group that received physiological saline, which was 187 [90] s (P = 0.03). Group variances were compared using an F test: onset time varied significantly less in the magnesium group (P = 0.02). CONCLUSION: In oncology patients of 60 or more years of age, preadministration of MgSO4, with the doses used in this study, significantly reduced the onset time of NMB induced by rocuronium. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01804205.

The effects of 6% hydroxyethyl starch-hypertonic saline in resuscitation of dogs with hemorrhagic shock.

BACKGROUND: Hemodynamic and global oxygen transport variables have failed to reflect splanchnic hypoperfusion, resulting in a failure to recognize inadequately treated hemorrhagic shock. Volemic expansion after fluid resuscitation is essential to improve global and regional oxygen in hemorrhagic shock. We hypothesized that, in contrast to conventional plasma expanders, the smaller volemic expansion from 7.5 NaCl/6% hydroxyethyl starch (HHES) solution administration in hemorrhagic shock may provide lesser systemic oxygen delivery and gastric perfusion. We used hemorrhaged dogs to compare intravascular volume expansion and the early systemic oxygenation and gastric perfusion effects of fixed fluid bolus administration, which are usually used in clinical situations with severe hemorrhage, of HHES, lactated Ringer (LR), and 6% hydroxyethyl starch (HES) solutions. METHODS: Thirty dogs were bled (30 mL · kg(-1)) to hold mean arterial blood pressure at 40 to 50 mm Hg over 45 minutes and were resuscitated in 3 groups: LR (n = 10) at 3:1 ratio to shed blood; HES (mean molecular weight 130 kDa, degree of substitution 0.4) (n = 10) at 1:1 to shed blood; and HHES (n = 10), 4 mL · kg(-1). Intravascular volume expansion (Evans blue and hemoglobin dilution), hemodynamic, systemic oxygenation, venous-to-arterial CO(2) gradient (Pv-aCO(2)), and gastric intramucosal-arterial PCO(2) gradient (PCO(2) gap) variables were measured at baseline, after 45 minutes of hemorrhage, and 5, 45, and 90 minutes after fluid resuscitation. RESULTS: HHES increased blood volume because of the high volume expansion efficiency, but intravascular volume expansion with this solution was the smallest of the solutions (P < 0.05). All 3 solutions induced a similar hemodynamic performance but HHES showed lower mixed venous PO(2) and higher systemic oxygenation extraction, Pv-aCO(2), and PCO(2) gap than LR and HES (P < 0.05). CONCLUSIONS: In dogs submitted to pressure-guided hemorrhagic shock and fixed-volume resuscitation, the smaller intravascular volume expansion from HHES solutions provides worse recovery of systemic oxygenation and gastric perfusion compared with LR and HES solutions despite its high volume expansion efficiency, which was limited by low infused volume.

Effect of esmolol on fluid therapy in normovolemia and hypovolemia.

beta-Adrenergic agonists can enhance vascular volume expansion after a fluid bolus. The present study addresses how the beta-adrenergic antagonist esmolol influences volume expansion and fluid balance during normovolemia (series 1) and hypovolemia (series 2). Sheep were instrumented, and the spleen was removed. For series 1, continuous infusion of 50 to 100 microg.kg(-1).min(-1) esmolol (n = 6) or control (no drug; n = 6) was begun 30 min before administration of a 24-mL kg(-1) 20-min bolus of 0.9% NaCl. For series 2, anesthetized sheep were infused with 50 to 100 microg.kg(-1).min(-1) esmolol (n = 6) or control (no drug; n = 6) 30 min before a-20 mL kg(-1) hemorrhage. Fluid resuscitation (0.9% NaCl) was begun 30 min after hemorrhage. The 24-mL kg(-1) 20-min bolus was followed by titrated fluid therapy. Hemoglobin, fluid in, and urinary output were used to calculate changes in plasma volume (DeltaPV), extravascular volume (DeltaEVV = fluid in - urinary output - DeltaPV), volume expansion efficiency (VEE = fluid in / DeltaPV), and fluid distribution ratio (DeltaPV/DeltaEVV). Hemodynamics for both series were similar with the exception of heart rate. In series 1, peak DeltaPV was 9.1 +/- 1.0 mL kg(-1) in control and 3.7 +/- 1.0 mL kg(-1) at study end. Esmolol resulted in a lower peak DeltaPV (6.4 +/- 2.0 mL kg(-1)) and a negative DeltaPV (-0.4 +/- 0.6 mL kg(-1)) at study's end. Urinary output was lower, and EVV was greater with esmolol. In series 2, esmolol increased fluid requirements (67 +/- 7 mL kg(-1)) compared with control (54 +/- 5 mL kg(-1)). Esmolol reduced DeltaPV/DeltaEVV. These data suggest that esmolol impairs the vascular retention of fluid and may increase the amount of volume support during fluid resuscitation.

Dexmedetomidine alters the cardiovascular response during infra-renal aortic cross-clamping in sevoflurane-anesthetized dogs.

Some properties of the volatile anesthetics, such as vasodilatation and myocardial depression, combined with the sympathetic inhibition that alpha2-agonists can produce, may determine hemodynamic alterations during aortic surgery. The interaction between dexmedetomidine (DEX), an alpha2-agonist, and sevoflurane during aortic surgery is unknown. We studied the effects of DEX on hemodynamics and systemic oxygenation during aortic cross-clamping (Aox) and unclamping (UAox) in sevoflurane-anesthetized dogs. Twenty dogs were anesthetized with sevoflurane and were randomly assigned to two groups prior to Aox and UAox: control, n = 10, received saline infusion only, and DEX (1 microg x kg(-1) load followed by 1 microg x kg(-1) x h(-1) infusion), n = 10. Hemodynamic and oxygenation variables were measured at baseline, after saline or DEX loading dose, 20 and 40 min after Aox, and 20 and 40 min after UAox. After DEX administration, heart rate, cardiac index (CI) and systemic oxygen transport index (DO(2)I) were lower than in control group. Aox increased mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) in both groups, but the effects were greater with DEX. CI, heart rate, and DO(2)I were lower, while central venous pressure (CVP) and pulmonary artery occlusion pressure were higher in DEX compared to control. After UAox, MAP, CVP and SVRI were maintained higher in DEX in relation to control. We conclude that in sevoflurane-anesthetized dogs DEX alters the cardiovascular response during aortic surgery.

Adrenergic drugs alter both the fluid kinetics and the hemodynamic responses to volume expansion in sheep.

BACKGROUND: Plasma volume expansion is often performed during adrenergic therapy in the intensive care unit, but little is known about their combined effects. MATERIALS AND METHODS: The influence of three adrenergic drugs (50 microg/kg/min of dopamine, 0.1 microg/kg/min of isoprenaline, or 3 microg/kg/min of phenylephrine) on the relationship between plasma dilution (an index of volume expansion) and the central hemodynamic responses to volume loading with 24 ml/kg of 0.9% saline were evaluated in 6 adult sheep. Kinetic analysis was also applied to the data on plasma dilution and the urinary excretion measured during and after volume loading. RESULTS: The adrenergic agents markedly changed the baseline values for all hemodynamic parameters. The kinetic analysis showed that phenylephrine, which is an alpha-adrenergic receptor agonist, promoted renal excretion of infused fluid at the expense of fluid distribution to the periphery (P < 0.05 versus controls). Isoprenaline, which stimulates adrenergic beta-receptors, had the opposite effect. During volume expansion, cardiac atrial pressures increased by 25 to 90%, cardiac output by 13-80% and the arterial pressures by 2 to 22%. Plasma dilution during and after volume loading correlated, in a linear fashion, with these hemodynamic responses. The correlations were strong (r > 0.80) in the control and phenylephrine groups, but weaker in the dopamine and isoprenaline groups. Dopamine was associated with the most variable hemodynamic responses overall. CONCLUSIONS: Adrenergic drugs altered the hemodynamics at baseline (direct effects), changed the distribution and elimination of infused 0.9% saline (indirect effects) and, finally, modified most hemodynamic responses to plasma dilution (interaction effects).

Effects of different catecholamines on the dynamics of volume expansion of crystalloid infusion.

BACKGROUND: The authors studied the influence of alpha, beta, and dopaminergic catecholamines on blood volume expansion in conscious normovolemic sheep before, during, and after a bolus infusion of a crystalloid. METHODS: A 0.9% NaCl bolus (24 ml/kg in 20 min) was infused in four paired experiments each: no drug, dopamine infusion (50 microg . kg . min), isoproterenol infusion (0.1 microg . kg . min), and phenylephrine infusion (3 microg . kg . min). Blood volume expansion was calculated by the dilution of blood hemoglobin concentration. RESULTS: Dopamine had little effect on peak blood volume expansion (12.7 +/- 0.9 ml/kg) compared with 0.9% NaCl (13.0 +/- 2.7 ml/kg); in contrast, isoproterenol augmented blood volume expansion (18.5 +/- 1.8 ml/kg), and phenylephrine reduced blood volume expansion (8.9 +/- 1.4 ml/kg). Two hours after the 0.9% NaCl bolus, sustained blood volume expansion was greatest in the isoproterenol protocol (12.2 ml/kg), whereas the dopamine protocol (6.8 ml/kg) remained similar to the control protocol (4.1 ml/kg), and the phenylephrine protocol had a net volume loss (-1.9 ml/kg). Some blood volume expansion differences were attributed to changes in renal function as phenylephrine infusion increased urinary output, whereas isoproterenol was associated with antidiuresis. However, dopamine caused diuresis and sustained augmentation of blood volume. CONCLUSION: Catecholamines can alter the intravascular volume expansion of fluid therapy. beta-Receptor (isoproterenol) stimulation augmented blood volume expansion, whereas alpha (phenylephrine) stimulation reduced blood volume expansion. Combined dopaminergic, beta, and possibly alpha stimulation with dopamine augmented blood volume expansion and cardiac output while inducing diuresis.

Comparison of transfusion with DCLHb or pRBCs for treatment of intraoperative anemia in sheep.

Isoflurane-anesthetized sheep were transfused with packed red blood cells (pRBCs) or diaspirin cross-linked hemoglobin (DCLHb) for treatment of intraoperative hemorrhage. A rapid 15-min hemorrhage with lactated Ringer (LR) infusion maintained filling pressure at baseline and reduced blood hemoglobin (Hb) to ~5 g/dl. Sheep received 2 g/kg Hb, DCLHb (n = 6), or pRBCs (n = 7); control group received LR alone (n = 6). After 2 h, anesthesia was discontinued; sheep were monitored in the animal intensive care unit for 48 h. DCLHb expanded blood volume more, but increased total blood Hb less, than pRBCs. Lower Hb and increased methemoglobin resulted in lower arterial oxygen content compared with the pRBCs. DCLHb caused pulmonary hypertension (from 13 to 30 mmHg) and elevated filling pressure (from 6 to 15 mmHg). Cardiac outputs (CO) were similar for all groups during anesthesia; however, during recovery CO increased only in the LR and packed pRBCs groups. DCLHb may limit the reflex ability to increase CO after volume expansion. Hemodynamic effects of DCLHb may be exaggerated when infused after large-volume LR.