The effect of preoperative methylprednisolone on pulmonary function and pain after lung operations.

Thirty-six patients undergoing elective thoracotomy with pulmonary resection with the use of combined epidural and general anesthesia were randomized into a double-blind study to receive a single intravenous preoperative dose of methylprednisolone 25 mg/kg body weight or a placebo (saline solution). Postoperative pain relief consisted of epidural morphine 4 mg and paracetamol 1 gm three times a day for 4 days. Postoperative pulmonary function (peak expiratory flow rate, forced expiratory volume in first second, forced vital capacity) was evaluated on days 1, 2, 3, 4, and 7 and after 1 month. The value obtained after 1 month served as the control value. Pain score at rest and during cough was evaluated after 4 and 8 hours and on days 1, 2, 3, and 4. Pulmonary function was reduced after operation to the same degree in the steroid and placebo group: 42% versus 41% for forced expiratory volume in first second and 38% versus 39% for forced vital capacity, compared with control values after 1 month. Pain score was reduced in the steroid group after 4 hours and on day 1 during rest and after 4 and 8 hours and on day 2 during cough, compared with results in the placebo group (p < 0.05). In the steroid group three patients underwent reoperation because of leakage through the chest wall incision. In conclusion, administration of a single preoperative dose of methylprednisolone did not affect the postoperative reduction in pulmonary function after thoracotomy despite attenuated pain response, and the results do not warrant steroid administration before lung operation.

Does the decrease in heart rate prevent a detrimental decrease of the end-systolic volume during central hypovolemia in man?

Central hypovolemia occurring with epidural anesthesia was investigated by measurement of hemodynamic and endocrine variables in 10 patients. Responses fell into two categories. Four patients experienced a hypotensive bradycardic episode after seventeen +/- four minutes. In this group epidural anesthesia initially induced a tendency toward an increase in heart rate from 65 +/- 4 to 73 +/- 5 beats/min concomitantly with decreases in end-diastolic (172 +/- 22 to 138 +/- 16 mL), end-systolic (67 +/- 12 to 51 +/- 9 mL), and stroke (105 +/- 10 to 85 +/- 7 mL) volumes (radionuclide cardiography). A subsequent decrease in mean arterial pressure from 76 +/- 3 to 67 +/- 4 mmHg was associated with a decrease in venous return as reflected by the decrease in cardiac output from 6.1 +/- 0.4 to 4.7 +/- 0.7 L/min. In this situation when the venous return was critically reduced, the heart rate was 49 +/- 4 beats/min and no further reduction in end-diastolic and end-systolic volumes was observed. The observed endocrine changes were compatible with a response to central hypovolemia. In the other 6 patients the reaction to epidural anesthesia did not induce statistically significant changes in hemodynamic and endocrine variables. It is concluded (1) that the decrease in heart rate associated with central hypovolemia during epidural anesthesia seems to be elicited when the left ventricular end-systolic volume is decreased by about 25% and (2) that a further decrease in end-systolic volume during progressive central hypovolemia is avoided possibly as a direct consequence of the slowing of the heart.

[Economic aspects of implementation of the mechanical heart, "HeartMate"]. / Okonomiske betragtninger ved implementering af det mekaniske hjerte, "HeartMate".

This economic evaluation was performed to assess the economic consequences for society and for the Danish health care sector of replacing the traditional treatment with Biomedicus assist device with The Mechanical Heart, HeartMate, as a bridge to transplantation for patients with severe cardiac failure. A cost-effectiveness analysis showed that the use of HeartMate is more cost-effective than the use of Biomedicus assist device. Using HeartMate one life-year gained costs DKK 225,000. Using Biomedicus one life-year gained costs DKK 270,000. The use of HeartMate results in an additional expenditure of DKK 615,000 per patient. By this additional expenditure the patients gain 3.6 extra life-years on average. The marginal expenditure by replacing the Biomedicus treatment with HeartMate is DKK 170,000 per extra life-year gained.

[Circulatory support with the mechanical heart, "HeartMate"]. / Cirkulationsstøtte med Det mekaniske hjerte, "HeartMate".

Treatment with the mechanical heart, HeartMate, has been introduced in Denmark. Short-term circulatory support can be obtained by intraaortic balloon counterpulsation, an external centrifugal pump and the total artificial heart. Long-term circulatory support can be established by treatment with the HeartMate. The principle of the mechanical heart is simple--a pump is implanted in parallel to the existing heart and connected to external, portable batteries. The patient quickly improves and is brought in an optimal state for transplantation. A few patients have been able to omit the subsequent heart transplantation. The patient's own heart improved during the treatment and the native heart functioned again after the system was explanted. The main complications during treatment are bleeding, infection, thromboembolic events and systemic failure. Permanent, fully implantable mechanical circulatory pumps are under development--which may herald the beginning of a whole new era for treatment of cardiac failure.

Vagal tone on the pancreatic polypeptide cell in duodenal ulcer patients. Correction for maximal and minimal secretory capacity.

It has previously been suggested that pancreatic polypeptide (PP) might serve as an indicator of abdominal vagal tone in duodenal ulcer (DU) patients. In this investigation we have attempted to study the vagal tone on the PP cells by correcting the basal PP concentrations to the insulin-stimulated (maximal) and atropine-suppressed (minimal) PP responses, to correct for the PP cell mass. There was no statistically significant difference between either the directly measured basal PP concentrations or the basal PP concentrations correlated to maximal and minimal secretory capacity in 10 DU patients and 10 sex- and age-matched controls. The observations indicate that the vagal branches to the PP cells of DU patients do not have higher tone than those of normal subjects.

Left atrial-aortic/femoral bypass with a centrifugal pump without systemic heparin during surgery on the descending aorta.

Active or passive bypass to support the distal circulation during cross-clamping of the descending thoracic aorta has been reported to decrease the incidence of paraparesis, to reduce left ventricle afterload, and to preserve distal organ perfusion. The aim of this study was to describe and to evaluate a perfusion technique for surgery on the descending aorta in humans. Nine patients underwent surgery on the descending thoracic aorta. The left atrium was cannulated using a Carmeda bioactive surface cannula. Distal cannulation sites were the left common femoral artery or the aorta below the involved segment. The cannulae were connected to a BioMedicus centrifugal pump via Carmeda bioactive surface tubings and pump heads. No systemic heparin was used. Cross-clamp time was 51 +/- 6 min, and the pump flow was 2.3 +/- 0.2 L/min. The mean arterial pressure in the upper body was 81 +/- 4 mm Hg and 68 +/- 5 mm Hg in the lower. Seven patients were discharged from hospital. Two patients with aortic rupture died; one died on the operating table, and the other, neurologically intact, died 4 days postoperatively due to multiorgan failure. No patients suffered spinal cord injury. It is concluded that active bypass without systemic heparin during cross-clamping of the descending aorta is simple and safe.

Heart and endocrine changes during central hypovolemia in man.

Animal experiments have shown that severe haemorrhage often is characterized by an initial general increase in sympathetic activity leading to an increase in heart rate and a subsequent vagally mediated, reversible decrease in heart rate. It is likely that the decrease in heart rate is triggered by mechanoreceptors situated in the left ventricle. The receptors are supposed to be activated by a reduction in end-systolic volume occurring as a result of a decrease in venous return concomitant with the initial increase in heart rate. SA vago-vagal reflex elicited from and returning to the heart is thereby activated, resulting in a slowing of the heart. It has been hypothesized that the left ventricular receptors are activated when the ventricle contracts around an almost bloodless chamber. The decrease in heart rate may allow for an increased filling of the heart and an improved coronary perfusion. However, these experimental observations are in clear contradiction to the general description of the regulatory mechanisms operating during haemorrhagic shock in man as presented by authoritative medical, surgical and anesthesiological textbooks. Until now the (over-simplified) notion has been, that progressive haemorrhage results in an increased activation of the sympathetic nervous system leading to an increase in heart rate and that the occurrence of bradycardia was a sign of irreversible shock. The present systematic measurements in patients in haemorrhagic shock showed that the heart rate during severe haemorrhage often was normal (mean value 73 beats/min, range 46-98 beats/min). Simultaneous measurements of plasma concentrations of pancreatic polypeptide (an index of vagal activity) indicated that organs other than the heart also were exposed to increased vagal activity. A marked increase in the plasma concentration of vasopressin was not a constant finding as it was during the experimental-induced hypotensive central hypovolemia. This difference may be due to a decline in the release of vasopressin during prolonged haemorrhage. In order to elucidate essential regulatory mechanisms behind the clinical observations, central hypovolemia was induced experimentally by "head-up tilt", "lower-body negative pressure", "venous tourniquets of the thighs plus haemorrhage", and by epidural anesthesia. The initial stage of central hypovolemia was characterized by an increase in sympathetic nervous activity resulting in an increase in heart rate. Activation of the renin-angiotensin-aldosterone system occurred prior to marked increases in plasma concentrations of vasopressin. During progression of the central hypovolemia a qualitative shift in the regulatory mechanisms was evident.(ABSTRACT TRUNCATED AT 400 WORDS)

Vagal slowing of the heart during haemorrhage: observations from 20 consecutive hypotensive patients.

Heart rate and arterial blood pressure were monitored in 20 consecutive patients during resuscitation from haemorrhagic shock. The mean blood loss (2.3 (SEM 0.3) 1) corresponded to 36(4)% of their estimated mean blood volume. During shock the mean blood pressure was 81/55 (3/2) mm Hg and heart rate 73 (3) beats/min. Administration of blood and crystalloids resulted in immediate increases to 111/72 (2/2) mm Hg and 102 (3) beats/min followed by steady state values of 131/79 (6/3) mm Hg and 82 (2) beats/min. In three otherwise healthy patients plasma concentrations of the vagally regulated hormone pancreatic polypeptide rose from resting values of 64-77 pmol/l (272-327 pg/ml) to 198-280 pmol/l (842-1190 pg/ml). These findings suggest that reversible hypotensive hypovolaemic shock is characterised by a decrease in heart rate conceivably reflecting an increase in vagal tone.

Biochemical markers for brain damage after cardiac surgery -- time profile and correlation with cognitive dysfunction.

BACKGROUND: Cerebral dysfunction is common after cardiac surgery and may be reflected in increasing blood concentrations of neuron specific enolase (NSE) and S-100 beta protein. The aim of the study was to determine the optimal timing of blood sampling. METHODS: We studied 15 patients undergoing coronary artery bypass grafting. Serum concentrations of NSE and S-100 beta protein were measured before surgery and after 12, 18, 24, 30, and 36 h. Neuropsychological testing was performed before surgery, at discharge from hospital and after 3 months. RESULTS: Serum concentrations of both NSE and S-100 beta protein increased significantly. At the first postoperative test, seven patients had cognitive dysfunction and a significant correlation was found between the composite z-score and the increase in the NSE level after 36 h (R = 0.76, P=0.001). The median increase in NSE after 36 h was 4.1 microg/l in patients having cognitive dysfunction and 0.9 microg/l in the remaining patients (P<0.05). No significant correlation was found between cognitive dysfunction and the increase in S-100 beta protein. After 3 months, no statistically significant correlation was found between either NSE or S-100 beta protein and cognitive dysfunction. CONCLUSION: NSE seems to be a useful blood marker for early cognitive dysfunction after coronary artery bypass grafting, optimal timing of blood sampling being at approximately 36 h postoperatively.

BioMedicus ventricular assistance for postcardiotomy heart failure: evaluation of univentricular assistance.

Clinical outcome and hemodynamic effects of unilateral mechanical ventricular support (UMVS) were evaluated in 19 patients with postcardiotomy heart failure refractory to conventional treatment. Adequate circulation with UMVS was maintained in about 75% of the patients. UMVS initiated circulatory stabilization in 5 of 6 patients with biventricular failure, in 2 of 3 patients with right ventricular failure, and in 7 of 10 patients with left ventricular failure. Eight (42%) patients were successfully weaned from UMVS and discharged from hospital. Six (32%) patients died despite a prolonged, stabilized circulation by UMVS. In 5 (26%) patients, the UMVS could not secure stable circulation. Application of the left UMVS induced increases in cardiac output and systemic blood pressure and a decrease in left atrial pressure without changes in pre- and afterload of the right ventricle. It is concluded that application of UMVS may induce adequate circulation in patients with postcardiotomy heart failure refractory to treatment with inotropes and intraaortic counterpulsation. The outcome of UMVS in left, right, and biventricular failure is acceptable. Thus, this treatment may be recommended for patients with postcardiotomy heart failure.

Sympathoadrenal and parasympathetic responses to exercise.

Exhaustive exercise is associated with a persistent sensation of weakness and sometimes nausea suggesting abdominal vagal activity. We measured plasma indices of sympathoadrenal (adrenaline, noradrenaline, dopamine) and vagal (pancreatic polypeptide) activity before, during and after submaximal and maximal exercise in healthy young subjects. Plasma adrenaline, noradrenaline and dopamine increased to 8.5 (range 7.4-40.5), 48.0 (32.3-100.5) and 1.8 (1.2-6.6) nmol 1-1 respectively (n = 5), during maximal exercise and decreased towards control values within 15 min of rest. Pancreatic polypeptide (n = 10) increased only during maximal exercise and reached its highest value, 48 (21-145) pmol 1-1, after exertion. The results conform to an increase in sympathetic activity during exercise and a persistent vagal activity after intense exercise which could contribute to the sensation of weakness.

Central venous pressure--a physiological stimulus for secretion of atrial natriuretic peptide in humans?

A sensitive radio-immunoassay (RIA) for the measurement of human alpha-atrial natriuretic peptide (ANP) in extracted plasma was developed and used in a study of the possible effect of posture on the concentration of ANP in plasma. The least detectable quantity was less than 2 pg per tube equivalent to 5 pg ml-1 plasma. In the middle sensitivity range (approximately 50 pg per tube), the within-assay and between-assay coefficients of variation were 4.0 and 2.8%, respectively. The recovery of ANP added to plasma prior to extraction was 95-101%. High pressure liquid chromatography (HPLC) of plasma extracts revealed that endogenous ANP was eluted in the same fractions as synthetic ANP. In order to investigate the effect of posture on the concentration of ANP in plasma six healthy volunteers were exposed to five positions in the following sequence: supine, standing, sitting, supine and 10 degrees head-down tilt on a tilt-table. The concentration of ANP was lower in the standing and sitting position than in the supine and head-down tilted position. In another study six healthy volunteers were subjected to passive tilting on a tilt-table in order to evaluate the effect of tilting on blood pressure (BP), heart rate, central venous pressure (CVP) and the concentration of ANP in plasma. It was found that a fall in CVP was accompanied by a significant decrease in the concentration of ANP and that a rise in CVP was accompanied by a rapid increase in the concentration of ANP in plasma. The results are in agreement with the hypothesis that CVP is a physiological stimulus for the secretion of ANP.

Angiotensin II attenuates reflex decrease in heart rate and sympathetic activity in man.

Circulatory variables and hormone concentrations in arterial plasma were measured in six normal subjects during angiotensin II (ANG II) step-up infusion of 0.25 and 1.00 ng kg-1 X min. During the 1.00 ng kg-1 X min infusion ANG II plasma concentrations increased from 11 +/- 2 to 48 +/- 6 pg ml-1; i.e., similar to those obtained during acute hypotensive hypovolaemia in man. Mean arterial pressure increased (P less than 0.05) from a resting value of 89 +/- 3 to 97 +/- 5 mmHg. Heart rate and catecholamine concentrations did not change. Plasma aldosterone increased (P less than 0.05) from 36 +/- 4 to 77 +/- 10 pg ml-1 during the infusion. Plasma concentrations of vasopressin, adrenalin and pancreatic polypeptide did not change during the investigation. During the 0.25 and 1.00 ng kg-1 X min infusion subcutaneous blood flow decreased (P = 0.06) to 67 +/- 20 and 66 +/- 26%, respectively, of control. It is concluded that: (1) ANG II in physiological doses in man may augment the sympathetic activity on the circulatory system since compensatory decreases in heart rate or in plasma catecholamines were not observed during the increased arterial pressure; (2) ANG II does not induce a general decrease in vagal tone as plasma pancreatic polypeptide concentrations were unchanged; (3) the obtained plasma concentrations of ANG II do not stimulate the release of vasopressin to plasma; and (4) the threshold for reducing the subcutaneous blood flow is reached within relatively small increments in plasma ANG II.

Progressive central hypovolaemia in man--resulting in a vasovagal syncope? Haemodynamic and endocrine variables during venous tourniquets of the thighs.

Hypotensive functional haemorrhage induced by venous pooling of blood in the legs has been reported to be characterized by a vasovagal reaction. In the present study these observations were extended by determination of the hormonal profile developed during progressive central hypovolaemia and an emotionally induced vasovagal syncope. In six subjects venous pooling resulted in normotensive central hypovolaemia, in one subject hypotensive central hypovolaemia was induced, and one subject experienced an emotionally induced vasovagal syncope. During normotensive central hypovolaemia heart rate increased from 58 +/- 4 to 76 +/- 4 beats min-1 (P less than 0.05) and cardiac output fell from 6.1 +/- 0.4 to 4.1 +/- 0.2 1 min-1. Pulse pressure and central venous pressure decreased from 64 +/- 4 to 53 +/- 4 mmHg, and from 8 +/- 2 to 3 +/- 2 mmHg, respectively. Adrenaline and noradrenaline increased from 87 +/- 10 to 120 +/- 20 pg/ml and from 196 +/- 33 to 370 +/- 50 pg/ml, respectively. Angiotensin II increased from 13 +/- 4 to 36 +/- 6 pg/ml and aldosterone from 63 +/- 9 to 180 +/- 27 pg/ml. In hypotensive central hypovolaemia the decrease in mean arterial pressure was accompanied by a decrease in heart rate and increments in the plasma concentrations of pancreatic polypeptide, indicating increased vagal activity and beta-endorphin, while plasma noradrenaline was unchanged. In emotionally induced syncope heart rate decreased to cardiac arrest for 13 s, associated with increments in the plasma concentrations of pancreatic polypeptide and beta-endorphin. It is concluded that normotensive functional haemorrhage in man is associated with increased sympathetic activity and that the qualitatively similar observations obtained during an emotionally and a hypovolaemic-induced hypotensive episode indicate that the hypotensive functional haemorrhage is characterized by a vasovagal reaction.

Hypotension induced by passive head-up tilt: endocrine and circulatory mechanisms.

Circulatory changes and arterial plasma hormone concentrations were measured in seven healthy young adults during 30 and 60 degrees passive head-up tilt with the subjects supported by a saddle. The 30 degrees tilt induced a decrease in pulse pressure (Pp) from 45 +/- 2 to 35 +/- 4 (mean +/- SE) mmHg concomitant with an increase in heart rate (HR) from 58 +/- 4 to 78 +/- 8 beats/min and a marginal increase in mean arterial pressure (MAP). Norepinephrine increased from 180 +/- 20 to 310 +/- 40 pg/ml, aldosterone increased fivefold, and angiotensin II increased from 8 +/- 2 to 22 +/- 7 pg/ml. The 60 degrees tilt initially produced changes, which were qualitatively similar to the 30 degrees tilt. However, after 19 +/- 3 min sudden decreases were seen in MAP (94 +/- 3 to 50 +/- 8 mmHg), in Pp (38 +/- 5 to 18 +/- 4 mmHg), and in HR (90 +/- 7 to 57 +/- 6 beats/min). Concomitantly, epinephrine doubled while norepinephrine remained unchanged; the vagally controlled hormone pancreatic polypeptide increased from 29 +/- 3 to 51 +/- 8 pmol/l, vasopressin from 4 +/- 1 to 126 +/- 58 pg/ml, and angiotensin II from 23 +/- 9 to 35 +/- 12 pg/ml. The hypotensive bradycardiac episode was immediately reversible on termination of the head-up tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in vagal activity during hypotensive lower-body negative pressure in humans.

Progressive central hypovolemia is characterized by a normotensive, tachycardic stage followed by a reversible, hypotensive stage with slowing of the heart rate (HR). We investigated circulatory changes and arterial hormone concentrations in response to lower-body negative pressure (LBNP) in six volunteers before and after atropine administration. LBNP of 55 mmHg initially resulted in an increase in HR from 55 +/- 4 to 90 +/- 5 beats/min and decreases in mean arterial pressure (MAP) from 94 +/- 4 to 81 +/- 5 mmHg, in central venous pressure from 7 +/- 1 to -3 +/- 1 mmHg, and in cardiac output from 6.1 +/- 0.5 to 3.7 +/- 0.11/min. Concomitantly, epinephrine and norepinephrine levels increased. After 8.2 +/- 2.3 min of LBNP, the MAP had decreased to 41 +/- 7 mmHg and HR had decreased to 57 +/- 3 beats/min. Vasopressin increased from 1.2 +/- 0.3 to 137 +/- 45 pg/ml and renin activity increased from 1.45 +/- 4.0 to 3.80 +/- 1.0 ng.ml-1.h-1 with no further changes in epinephrine, norepinephrine, and vasoactive intestinal polypeptide. A tardy rise in pancreatic polypeptide indicated increased vagal activity. After atropine. LBNP also caused an initial increase in HR, which, however, remained elevated during the subsequent decrease in MAP to 45 +/- 6 mmHg occurring after 8.1 +/- 2.4 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Bradycardia during severe but reversible hypovolemic shock in man.

Severe bleeding and hypovolemic shock causing hypotension are most often associated with tachycardia. In response to passive head-up tilt, five healthy men exhibited an increase in heart rate (HR) from 62 to 79 beats X min-1 and a gradual increase in the plasma concentration of aldosterone and protein. The increase in HR was followed by a decrease of 29 beats X min-1 (range 11-46) at the time when blood pressure decreased 38 mmHg (6-73). When tilted back to 0 degree, blood pressure immediately reversed while HR remained unchanged. Hypotension was associated with large but variable increases in plasma vasopressin (86 +/- 28 pg X ml-1) accompanied by peripheral vasoconstriction. In two cases where patients with internal bleeding presented with a moderate HR of 96 beats X min-1, the ensuing fall in blood pressure was associated with a decrease in HR to 68 and 76 beats X min-1, respectively. Administration of albumin solution and blood normalized cardiovascular function. Two other patients showing initial HR of 130 and 100 beats X min-1, respectively, also developed relative bradycardia in conjunction with a decrease in blood pressure. Administration of ephedrine and atropine increased HR temporarily from 56 to 90 and from 36 to 110 beats X min-1, respectively. The latter two patients died in extreme bradycardia and autopsies revealed severe internal bleeding. It is concluded that although hypovolemic shock is most often associated with an increase in HR, the increase is modest and a paradoxical bradycardia develops in severe but potentially reversible hypotensive hypovolemic shock.