Effects of propofol vs methohexital on neutrophil function and immune status in critically ill patients.

PURPOSE: Patients with severe brain injury often require long-term sedation and have a high incidence of nosocomial infections, causing an increased mortality rate. However, whether anesthetic drugs might contribute to immunosuppressive effects remains unclear. METHODS: In this prospective study, we investigated the effects of propofol (4-6 mg x kg(-1) x h(-1)) and methohexital (1-3 mg x kg(-1) x h(-1)) on neutrophil leukocyte function and immune status in 21 patients with brain injury who either received propofol (n = 12; 9 male, 3 female; mean age, 51 +/- 15 years) or methohexital (n = 9; 8 male, 1 female; mean age, 48 +/- 17 years) after admission to the intensive care unit (ICU). Both sedatives were administered over 7 days and individual dosage was adapted according to clinical requirements. Neutrophil leukocyte function was assessed as phagocytosis and respiratory oxidative burst activity. Furthermore, leukocyte subpopulations, and surface markers of lymphocytes and monocytes (CD3; CD4; CD45RO; CD4/CD45RO; CD25; CD4 and CD25; CD54; CD69; CD14/HLA-DR; CD8; CD3/HLA-DR; CD4 : CD8 ratio) were assessed. Blood samples were drawn on ICU admission, and on days 3, 7, and 14. Patients' demographics were compared by Wilcoxon test and laboratory results were compared by analysis of variance (ANOVA) for repeated measurements, with an all pairwise multiple comparison procedure. RESULTS: There were no significant differences in neutrophil oxidative burst and phagocytosis within or between the two groups at the different time points. With respect to cellular markers of lymphocytes and monocytes, all values throughout remained in the normal range. CONCLUSION: Methohexital and propofol exhibited no significant effects on neutrophil function and immune status in patients with severe brain injury requiring long-term sedation.

Anaesthesia and anti-cancer chemotherapeutic drugs.

PURPOSE OF REVIEW: This is a review of anti-cancer chemotherapeutic drugs, describing their actions, interactions, and toxicity with a particular focus on the relevance for the anaesthetist. RECENT FINDINGS: Anti-cancer chemotherapeutics have a vast array of adverse effects, some of which, i.e. cardiac and pulmonary toxicity, are of particular anaesthesiological relevance. Recently it has been shown that following chemotherapy with anthracyclines subtle abnormalities in cardiac function may exist even in those patients with a normal resting cardiac function, which become apparent only during anaesthesia or exercise. Children and adolescents with previous anthracycline treatment and normal cardiac function at rest had a significantly greater decrease in fractional shortening, a marker of left-ventricular systolic function, and stroke-volume index during a balanced anaesthesia with isoflurane [1 minimum alveolar concentration (MAC)] in N2O/O2. Notably, delayed cardiotoxicity (years after completed chemotherapy) has been seen only after anthracycline therapy. With respect to regional anaesthetics, one should be aware that in a considerable percentage of patients a sub-clinical, unrecognized neuropathy may be present in patients with previous chemotherapy, particularly after cisplatin treatment. Recently, a diffuse brachial plexopathy after interscalene blockade has been reported in a patient receiving cisplatin chemotherapy. Thus, if regional anaesthesia is contemplated, a detailed pre-operative neurological examination and careful assessment of the risks and benefits is warranted. SUMMARY: Anti-cancer chemotherapeutic drugs may cause generalized and specific organ toxicities and may also give rise to various unpredictable or life-threatening peri-operative complications, rendering a detailed pre-operative assessment of patients with previous chemotherapy mandatory.

The influence of anthracycline therapy on cardiac function during anesthesia.

UNLABELLED: Cardiotoxicity is a well recognized complication of anthracycline (AC) therapy. Subtle abnormalities in myocardial function that become apparent only after exercise may exist in survivors of childhood cancer who have previously received AC, yet have normal resting cardiac function. To evaluate if anesthesia-induced changes in cardiac function differ in pediatric patients with previous AC therapy from healthy children and adolescents, we evaluated in a prospective study 43 patients, of whom 42 were analyzed. Twenty-one patients (AC-group), mean age 9.6 yr (range, 3-16 yr), who had received 193 (30-490) mg/m(2) of AC as a mean cumulative dose with normal resting cardiac function (shortening fraction [SF] 0.34, normal value > 0.30) underwent removal of a Hickman catheter under general anesthesia. Twenty-one patients, mean age 10.9 yr (range, 4-17 yr), who underwent placement of a Hickman catheter before chemotherapy served as the control. All children were premedicated with midazolam 0.5 mg/kg orally. Anesthesia was induced by sodium thiopental (5 mg/kg), fentanyl (3 micro g/kg), and rocuronium (0.6 mg/kg) and maintained with isoflurane (1 MAC) in N(2)O/O(2) (70/30). Before induction (baseline), 5 and 20 min after intubation (T1 and T2), and 20 min after extubation (control), cardiac function was assessed by transthoracic (baseline, control) and transesophageal (T1, T2) echocardiography. Compared with baseline (SF: 34.9 +/- 3.7 [AC], 34.1 +/- 3.7 [C] [not significant]; stroke volume index [SVI] 36 +/- 6 mL/m(2)[AC], 35 +/- 4 mL/m(2)[C] [not significant]; cardiac index [CI] 3.6 +/- 0.6 L/min/m(2)[AC], 3.2 +/- 0.5 L/min/m(2)[C] [not significant]), we found a significant decrease in SF and SVI in both groups at T1 (SF: 26.2 +/- 3.6 [AC] versus 28.6 +/- 3.6 [C] [P < 0.05]; SVI: 26 +/- 4 mL/m(2) [AC] versus 30 +/- 46 mL/m(2) [C] [P < 0.05]) and T2 (SF: 24.1 +/- 3.2 [AC] versus 28.2 +/- 2.5 [C] [P < 0.01], SVI: 26 +/- 6 mL/m(2) [AC] versus 31 +/- 5 mL/m(2) [C] [P < 0.01]), which was significantly greater in the AC group. There were no significant changes of variables of diastolic function (E/A ratio, isovolumetric relaxation time) between both groups. Previous treatment with AC may enhance the myocardial depressive effect of anesthetics even in patients with normal resting cardiac function. IMPLICATIONS: Previous treatment with anthracylines, a group of chemotherapeutic drugs in use for childhood cancer, may enhance the myocardial depressive effect of anesthetics even in children and adolescents with normal resting cardiac function.

Preserved CO(2) reactivity and increase in middle cerebral arterial blood flow velocity during laparoscopic surgery in children.

UNLABELLED: In adult patients, the creation of pneumoperitoneum (PP) by means of carbon dioxide (CO(2)) insufflation leads to an increase in cerebral blood flow velocity (CBFV), which is thought to be caused by hypercapnia. We evaluated whether PP leads to an increase of CBFV in children, and whether this increase is directly related to PP. The effects of PP on middle cerebral artery blood flow velocity were investigated in 12 children (mean age 3 yr, range 15-63 mo) undergoing laparoscopic herniorrhaphy under general anesthesia with sevoflurane and nitrous oxide/oxygen. CBFV was measured by using transcranial Doppler ultrasonography. During CO(2) insufflation, the end-tidal CO(2) concentration was kept constant by adjustment of ventilation by increasing minute volume. The CBFV increased significantly at an intraabdominal pressure of 12 mm Hg compared with baseline from 68 +/- 11 cm/s to 81 +/- 12 cm/s (P < 0.05). CO(2) reactivity remained in the normal range (4.0% +/- 1.9%/mm Hg) during PP. We conclude that the induction of PP leads to an increase in middle cerebral artery blood flow velocity in young children independent from hypercapnia, whereas CO(2) reactivity remains normal. IMPLICATIONS: Laparoscopic surgery is performed frequently in pediatric patients. Cerebral blood flow velocities increase during insufflation of the intraperitoneal cavity for minimally invasive surgery in children. The vasoreactivity as part of the cerebral autoregulation remains unaffected.