Effect of ischemic preconditioning on myocardial protection in coronary artery bypass graft patients : can the free radicals act as a trigger for ischemic preconditioning?

OBJECTIVE: To investigate the interrelationship of free radicals (FRs), ischemic preconditioning (IP), and hemodynamic function in coronary artery bypass graft (CABG) patients. DESIGN: Prospective, randomized, and controlled clinical study. PATIENTS: Forty CABG patients were randomized into an IP group (n = 20) and a control group (n = 20). INTERVENTION: The IP group was preconditioned with two cycles of two-min ischemia followed by 3-min reperfusion before cross-clamping. MEASUREMENT AND RESULTS: FR content in coronary sinus blood was measured directly using alpha-phenyl-N-tert-butylnitrone-electron spin-trapped spectroscopy. A small amount of FRs was generated after the IP protocol (5.6% above the baseline) but not in control subjects. A larger amount was generated 10 min after declamping in both groups (8.4% in IP protocol and 7.7% in control subjects). Hemodynamic function recovered better in the IP group at 1 h and 6 h after declamping. There was a significant negative correlation between FR generation after declamping and left ventricular stroke work index (LVSWI) at 1 h and 6 h after declamping (r = -0.71 and - 0.59, respectively) in the control subjects but not in the IP group. There was a significant positive correlation between FR generation after the IP protocol and cardiac index at 1 h and 6 h (r = 0.50 and 0.61, respectively) and LVSWI at 1 h and 6 h (r = 0.56 and 0.54, respectively) after declamping in the IP group but not in the control subjects. CONCLUSION: FR generation after the operation correlates with ventricular functional depression in CABG patients. IP protects the stunning heart but does not alter FR generation. The association of better hemodynamic recovery after CABG with FR generation during the IP period suggests that FRs might act as one of the triggers for IP.

The protective effects of preconditioning decline in aged patients undergoing coronary artery bypass grafting.

OBJECTIVE: We sought to investigate the effects of myocardial ischemic preconditioning in adult and aged patients undergoing coronary artery bypass grafting. METHODS: Eighty patients with 3-vessel disease undergoing coronary artery bypass grafting were randomized into one of the following groups: adult ischemic preconditioning, adult control, aged ischemic preconditioning, and aged control. Hemodynamic data and cardiac troponin I values were compared between the groups. The ischemic preconditioning groups received 2 periods of 2 minutes of ischemia, followed by 3 minutes of reperfusion. The Student t test, chi(2) test, and analysis of variance for repeated measures were used for the statistical analysis. RESULTS: The baseline for right ventricular ejection fraction and cardiac index was similar. Right ventricular ejection fraction was depressed after the operation in all groups. Ischemic preconditioning significantly improved the recovery of right ventricular ejection fraction and cardiac index after the operation in adult patients (P =.013 and.001, respectively), but in the aged group there was no difference in the changes of ejection fraction and cardiac index (P =.232 and.889, respectively). The cardiac troponin I value in the adult patients subjected to ischemic preconditioning was lower than that in the adult control subjects (P =.046), but in aged patients undergoing ischemic preconditioning, the value was similar to that in aged control subjects (P =.897). Ischemic preconditioning also resulted in a shorter postoperative mechanical ventilation time and in less inotropic use in the adult group. CONCLUSION: Ischemic preconditioning protects the heart from ischemic reperfusion injury in adult patients undergoing coronary artery bypass grafting. The beneficial effects of ischemic preconditioning are manifested as a better recovery of right ventricular and global hemodynamic function, cellular viability, and surgical outcome. The protective effect of ischemic preconditioning is diminished in aged patients undergoing coronary bypass.

Current practice regarding invasive monitoring in intensive care units in Finland. A nationwide study of the uses of arterial, pulmonary artery and central venous catheters and their effect on outcome. The Finnish Intensive Care Study Group.

As part of a nationwide evaluation of intensive care, we examined patient- and hospital-related factors which could influence the patterns of utilization of arterial cannulae and central venous and pulmonary artery catheters. We also studied the possible impact of these interventions on the short-term outcome among 14,951 consecutive ICU admissions to 25 intensive care units (75% of all ICU beds) in Finland. There was considerable variation between individual units in the use of these devices even if the differences in severity of illness were taken into account. Arterial cannulation was used in 71.2%, PA catheterization in 10.6% and CVP monitoring in 49.3% of cases in teaching ICUs, excluding cardiac surgery, and in 38.5%, 2.6% and 33.1% of cases in non-teaching ICUs respectively. The factors predicting the use of invasive monitoring included extensive surgery causing a risk of cardiovascular instability, needs for mechanical ventilation, infusion of vasoactive drugs and complicated fluid therapy. Cardiovascular problems among non-operative patients increased the odds for PA catheterization but reduced them for arterial and CV cannulation. No clear-cut benefit could be found in the form of hospital mortality reduction from invasive haemodynamic monitoring, used as described in this study.

Contribution of non-neurologic disturbances in acute physiology to the prediction of intensive care outcome after head injury or non-traumatic intracranial haemorrhage.

OBJECTIVE: To study the additional contribution of non-neurologic disturbances in acute physiology and chronic health to the prediction of intensive care outcome in patients with head injury or non-traumatic intracranial haemorrhage. DESIGN: A nationwide study in Finland with prospectively collected data on all adult patients admitted to intensive care after head trauma or non-traumatic intracranial haemorrhage during a 14-month period. Two-thirds of the patients were randomly selected to derive predictive models, and the remaining one third constituted the validation sample. SETTING: A total of 25 medical and surgical ICUs in Finland (13 in tertiary referral centers). PATIENTS: 901 consecutive adult patients with head injury or non-traumatic intracranial haemorrhage. MEASUREMENTS AND RESULTS: Variables of the APACHE II including Glasgow Coma Score were collected at the time of ICU admission. Two predictive models were created to explain hospital mortality. The addition of variables describing acute physiology to a predictive model consisting of Glasgow Coma Score, age, diagnosis of head injury and the type of ICU admission did not increase its performance in discriminating between survivors and nonsurvivors, but the calibration accuracy of the predictive model especially at the high ranges of risk was improved. CONCLUSIONS: The non-neurologic disturbances in acute physiology have prognostic significance in the prediction of intensive care outcome in patients with head injury or non-traumatic intracerebral haemorrhage. The created predictive model may supplement clinical judgement of this patient group.

Plasma thromboxane B2 levels and thromboxane B2 production by platelets are increased in patients during spinal and epidural anesthesia.

Concentrations of thromboxane (Tx) B2 in plasma and its production by platelets were measured in 20 spinal and 10 epidural anesthesia patients scheduled for small operations in the lower extremities. The main metabolite of prostacyclin, 6-keto-PGF1 alpha and prostaglandin (PG) E2 in plasma were also determined. Plasma TxB2 and TxB2 production by platelets increased during both spinal and epidural anesthesia. Plasma TxB2 levels also remained elevated 1 h after anesthesia. The plasma concentrations of 6-keto-PGF1 alpha and PGE2 did not change during spinal or epidural anesthesia. In in vitro studies, only low concentrations of lidocaine (0.5-1.0 micrograms/ml) and bupivacaine (0.5-3.0 micrograms/ml) increased platelet TxB2 production. In platelet rich plasma, neither lidocaine nor bupivacaine in concentrations of 0.5-3.0 micrograms/ml caused constant changes in ADP-induced platelet aggregation, but they inhibited it in toxic concentrations (12 micrograms/ml). The results suggest that the increased TxB2 plasma levels and platelet TxB2 production during regional anesthesia are not caused by local anesthetics itself but by other factors, e.g. tissue trauma. In clinically found concentrations, local anesthetics do not cause any constant changes in platelet aggregation.

Beneficial effects of ischemic preconditioning on right ventricular function after coronary artery bypass grafting.

BACKGROUND: Preservation of right ventricular myocardium is unsatisfactory in patients with critical stenosis or occlusion of the right coronary artery. The aim of this study was to investigate whether ischemic preconditioning (IP) improved the recovery of right ventricular function after coronary artery bypass grafting. METHODS: Forty patients with three-vessel disease who had coronary artery bypass grafting were randomly assigned to the IP group (n = 20) or control group (n = 20). In the IP group, two cycles of two minutes of ischemia after three minutes of reperfusion were given before cross-clamping. Hemodynamic data were collected. Right ventricular ejection fraction was measured by thermodilution. RESULTS: Right ventricular ejection fraction and right ventricular systolic volume index were decreased post-operatively (lowest value at 6 hours postoperatively). The changes in right ventricular ejection fraction were significantly milder in the IP group postoperatively (p = 0.012). The decrease in right ventricular systolic volume index postoperatively was also less in IP patients (p = 0.002). Fewer inotropic drugs were used in the IP group compared with controls. CONCLUSIONS: Ischemic preconditioning had a myocardial protective effect on recovery of right ventricular contractility in patients who had coronary artery bypass grafting.

Fluid resuscitation of hypotensive emergency patients with and without an algorithm.

Seventy-seven consecutive hypotensive (mean arterial pressure (MAP) less than 80 mmHg) surgical emergency patients were resuscitated according to either physicians' individual orders (38 patients) or an algorithm (39 patients). The shock was mainly caused by accidental injuries or acute gastrointestinal bleeding. The patients of the algorithm group were given more plasma expanders than the patients of the control group, while the total amount of fluids administered was similar in both groups. The primary goal of the resuscitation (MAP greater than 80 mmHg) was reached within 30 min in three cases in the control group and in seven cases in the algorithm group. The treatment times at the emergency department and the intensive care unit were similar for the groups. The number of severe and moderate pulmonary disturbances was the same, but mild disturbances were significantly more common in the control group. Renal failure was somewhat more common in the control group and the renal function disturbances were significantly more severe among the control patients. The results suggest that the physicians in some extent altered their practices in fluid resuscitation when the algorithm was put to use, and that this change, perhaps, produced the somewhat better outcome of the patients. The authors recommend the algorithm to be used as a basis of shock treatment and particularly in those emergency departments where the resuscitation of hypotensive patients is performed by junior or inexperienced physicians.

Ischemic preconditioning protects right ventricular function in coronary artery bypass grafting patients experiencing angina within 48-72 hours.

BACKGROUND: To test whether ischemic preconditioning (IP) is able to protect the myocardium in recently unstable CABG patients. EXPERIMENTAL DESIGN: prospective, randomised, controlled clinical study. SETTING: University Hospital. PATIENTS: Forty CABG patients with recent unstable angina were randomised into an IP group (n=20) and a control group (n=20). Subgroup was divided based on the time of the most recent ischemia onset before the operation. INTERVENTION: The IP group was preconditioned with 2 cycles of 2-min ischemia followed by 3-min reperfusion before cross clamping. MEASURES: Hemodynamic data were monitored till the 1st POD. Biochemical markers were measured till the 2nd POD. RESULTS: There were no differences in cardiac index (Cl) and right ventricular ejection fraction (RVEF) in patients experiencing angina within 48 hours prior to operation. The percentage changes in CI and RVEF at 1 hour after declamping were significantly better in the IP group in patients experienced angina within 48-72 hours (106% vs 88% of baseline, p=0.027 and 103% vs 81% of baseline, p=0.023). No difference in postoperative cardiac troponin I (CTnI) and CK-MB was found between the IP and controls in either subgroup. CONCLUSIONS: IP has a beneficial effect on global and right ventricular hemodynamic functional recovery in unstable CABG patients experiencing angina within 48-72 hours prior to the operation. However, IP has no additional protective effects in unstable CABG patients who experience angina within 48 hours.

Results of intensive care in abdominal surgery patients.

A one-year follow-up of 300 consecutive critically ill abdominal surgery patients treated in an intensive care unit is presented. 77 patients (26%) died during intensive care. By the end of the follow-up period altogether 139 patients (47%) had died from the primary disease. Almost all patients who died after intensive care, did so within the first month. The majority of the survivors (124 patients) recovered completely, most of them within six months after intensive care. Only 22 patients remained incapable of their previous work, and five became permanently disabled. Mortality rates were at their lowest in diseases of the pancreas (34%), the stomach and duodenum (43%) and of the liver and gall bladder (44%), if cirrhosis with ruptured oesophageal varices is excluded; here the mortality was highest, 76%.

Clinical course and prognostic signs in near-drowned patients.

The clinical course and outcome of 49 consecutive near-drowned patients is presented. All the immersions occurred in fresh water. 37 patients (76%) survived. All 28 patients who were conscious upon admission to hospital recovered fully. However, 13 of these developed pulmonary infiltrates on chest X-ray, three of them with severe respiratory distress syndrome (ARDS) requiring respirator treatment. On entering the emergency station 16 patients had cardiac arrest. 15 of these were successfully resuscitated, of whom, however, 11 died later, most from hypoxic brain damage. Among unconscious patients, the non-survivors had on arrival an average lower rectal temperature than the survivors. The following factors during intensive care correlated with bad prognosis: low PaO2/FiO2, low serum protein concentration and disturbances in renal function. Furthermore, the findings of this study suggest that although a specific near-drowned patient has on admission most abnormal laboratory values, these do not predict his fate, but effective treatment has to be given.

[The harmful effects of beta2-sympathomimetic drugs as uterine relaxants on caesarean section (author's transl)]. / Nachteilige Wirkungen der Beta2-Sympathikomimetika als Tokolytika bei Sectio caesarea.

Beta2-sympathomimetics are the most powerful inhibitors of uterine contraction used in order to prevent threatening fetal asphyxia. These drugs, however, can cause harmful interactions with anaesthetics during caesarean section. Our patient-material consists of parturients, who were given a beta2-sympathomimetic, ritodrine, immediately before caesarean section performed under combined general anaesthesia. These patients showed significantly more marked tachycardia, hypotonia and abundant haemorrhage during operation as a consequence of poor uterine contractility than did the control group. Rapid variations in the circulation of the mother may also be disadvantageous to the wellfare of the fetus. These side-effects can best be minimized by omitting atropine-premedication and by expanding the blood volume of the mother before caesarean section with adequate infusion of Ringer-type.

Prognostic signs in abdominal surgery patients treated in the intensive care unit.

To determine which factors had correlation with mortality during intensive care, 300 consecutive admissions to the intensive care unit in 286 critically ill patients requiring abdominal surgery were analyzed. The follow-up was one year. On admission, before any treatment was given, disturbances of vital functions (circulation, respiration, fluid- and acid-base balance, renal function, consciousness and other special disturbances) were classified into three grades according to their severity. The increase in the grade of severity, or especially in the sum of the grades of disturbances in various vital functions, correlated well with the mortality rate. Deviations in several biochemical parameters (e.g. serum sodium and potassium concentrations and serum osmolality) during intensive care were associated with an increase in mortality rate, even where these parameters were abnormal for only a short time and were later brought within normal range. With stepwise multiple discriminant analysis of model including 13 variables was formed to identify survivors and nonsurvivors. The strongest predictors of fatal outcome in this analysis were cirrhosis, increasing are and the sum of severity grades of disturbances in vital functions on admission.

The mechanism of Nissen fundoplication.

Six patients with objectively proven reflux oesophagitis were studied in association with fundoplication. Intraoperative manometry was performed with a conventional station-pull-through technique, using a constantly perfused catheter (1 ml/min) with four side holes. The drugs used for general anaesthesia did not influence the lower oesophageal sphincter. The lower oesophageal pressure was measured before and after fundoplication, after filling the stomach with 200 ml of air, and after gastric compression. The rise in lower oesophageal pressure after fundoplication varied widely, from 1 to 25 (mean 10) mmHg. After the gastric compression, the oesophageal pressure rise (mean 7, range 3-11 mmHg) corresponded to the increase in intragastric pressure (mean 6, range 4-8 mmHg). The results of the study suggested that the tightening effect of fundoplication on the distal oesophagus may not explain the antireflux mechanism of the operation. Instead the fundoplication seems to function as a flutter-valve.

Epidural anaesthesia with mixtures of bupivacaine-lidocaine and etidocaine-lidocaine.

The mixtures of 0.5% bupivacaine- 1% lidocaine and 1% etidocaine- 1% lidocaine were used in a double-blind manner for lumbar epidural anaesthesia in 48 patients undergoing prostatectomy in order to study whether these mixtures speed up the onset of analgesia, shorten the long motor block, motor block, or improve the quality of analgesia caused by bupivacaine or etidocaine alone. The mixture of bupivacaine-lidocaine caused an analgesia with a somewhat faster onset, similar duration and markedly shorter motor block than bupivacaine alone. The sensory block produced by the mixture of etidocaine-lidocaine tended to begin more slowly and had a distinctly shorter duration, as was the motor block, as compared to the block caused by etidocaine alone. The analgesia was complete in all 12 patients who received bupivacaine and in 11/12 patients who received the mixture of bupivacaine-lidocaine, but 6/12 patients anaesthetized with etidocaine and 5/12 patients with the mixture of etidocaine-lidocaine experienced considerable visceral pain during the operation. The results suggest that the mixture of bupivacaine-lidocaine produces a block with somewhat better properties than bupivacaine alone, but the mixture of etidocaine-lidocaine does not offer any advantages as compared to etidocaine alone, except the shorter motor block.

Fatal brain lesion following spinal anaesthesia. Report of a case.

Leakage of cerebrospinal fluid following dural puncture and subsequent downward sagging of the brain have been suggested as a cause of the rare subdural haematomas occurring after spinal or attempted epidural anaesthesia which have been reported in the literature. We report a case where this mechanism probably produced a fatal brain lesion, due to the herniation of the uncus against the tentorium cerebelli 15 days after spinal anaesthesia. The patients complained of severe headache and nausea after the procedure. The reported case shows that postdural-puncture headache may be a sign of more serious sequelae and should be treated by the means available.

[Epidural anesthesia with carticaine in cesarean section. A comparison with bupivacaine]. / Epiduralanaesthesie mit Carticain bei Sectio caesarea. Ein Vergleich mit Bupivacain.

The feasibility of 1.5% carticaine, an amide-type local anaesthetic agent, for epidural anaesthesia for Caesarean section was studied in 15 parturients. As a control, epidural anaesthesia in 15 parturients was done with 0.5% bupivacaine. The quality of anaesthesia before delivery was good in both groups. One additional dose of carticaine had to be given after delivery in order for the anaesthesia to last until the end of the operation. Apgar-scores, maternal and fetal pH and blood-gas values were similar in both groups. Maternal arterial serum concentration of bupivacaine at the time of delivery was 1.25 microgram/ml, while that of carticaine was only 0.48 microgram/ml. The lower serum concentration of carticaine is due to its rapid metabolization. The ratio of the unmetabolized drug to that of the metabolite found in maternal serum at the time of delivery was 0.75. Umbilical venous-maternal arterial serum concentration ratio in bupivacaine patients was 0.28 and in carticaine patients 0.32. The results suggest that carticaine is a feasible drug for Caesarean section.

Prognostic indicators in burned patients.

The clinical course and outcome of 64 burned patients treated in the intensive care unit were analysed in order to find indicators for prognosis. Total burn area varied from 7 to 90% of body surface area. 17 patients (27%) died. In addition to the extent of burn injury and nature of it, e.g. airway burns, disturbances in some biochemical parameters were associated with increased mortality. These were disturbances in haematocrit, thrombocyte numbers, arterial pH, serum protein concentration and serum osmolality during the first three days of treatment. By means of a logistic model factors were obtained which proved most significant for prognosis; these were the age of the patient, arterial pH and serum protein concentration at the beginning of the treatment. The results suggest that the extent of the burned area is not the only factor affecting the outcome of the patient.