Increased Mortality Despite Successful Multifactorial Cardiovascular Risk Reduction in Healthy Men: 40-Year Follow-Up of the Helsinki Businessmen Study Intervention Trial.

OBJECTIVES: In a 5-year multifactorial risk reduction intervention for healthy men with at least one cardiovascular disease (CVD) risk factor, mortality was unexpectedly higher in the intervention than the control group during the first 15-year follow-up. In order to find explanations for the adverse outcome, we have extended mortality follow-up and examined in greater detail baseline characteristics that contributed to total mortality. DESIGN: Long-term follow-up of a controlled intervention trial. SETTING: The Helsinki Businessmen Study Intervention Trial. PARTICIPANTS AND INTERVENTION: The prevention trial between 1974-1980 included 1,222 initially healthy men (born 1919-1934) at high CVD risk, who were randomly allocated into intervention (n=612) and control groups (n=610). The 5-year multifactorial intervention consisted of personal health education and contemporary drug treatments for dyslipidemia and hypertension. In the present analysis we used previously unpublished data on baseline risk factors and lifestyle characteristics. MAIN OUTCOME MEASURES: 40-year total and cause-specific mortality through linkage to nation-wide death registers. RESULTS: The study groups were practically identical at baseline in 1974, and the 5-year intervention significantly improved risk factors (body mass index, blood pressure, serum lipids and glucose), and total CVD risk by 46% in the intervention group. Despite this, total mortality has been consistently higher up to 25 years post-trial in the intervention group than the control group, and converging thereafter. Increased mortality risk was driven by CVD and accidental deaths. Of the newly-analysed baseline factors, there was a significant interaction for mortality between intervention group and yearly vacation time (P=0.027): shorter vacation was associated with excess 30-year mortality in the intervention (hazard ratio 1.37, 95% CI 1.03-1.83, P=0.03), but not in the control group (P=0.5). This finding was robust to multivariable adjustments. CONCLUSION: After a multifactorial intervention for healthy men with at least one CVD risk factor, there has been an unexpectedly increased mortality in the intervention group. This increase was especially observed in a subgroup characterised by shorter vacation time at baseline. Although this adverse response to personal preventive measures in vulnerable individuals may be characteristic to men of high social status with subclinical CVD, it clearly deserves further investigation.

Association of midlife obesity and cardiovascular risk with old age frailty: a 26-year follow-up of initially healthy men.

OBJECTIVE AND HYPOTHESIS: To investigate whether old age frailty is predicted by midlife overweight/obesity and cardiovascular disease (CVD) risk. DESIGN: Longitudinal observational study (the Helsinki Businessmen Study). SUBJECTS: In their midlife in 1974, 1815 initially healthy men (mean age 47 years) were clinically investigated, whereupon their weight status (normal weight < 25 kg m(-2), overweight 25 ≤ body mass index <30 kg m(-2) and obese ≥ 30 kg m(-2)), CVD risk factors and a composite risk score (%) of coronary artery disease (CAD) were assessed. After a 26-year follow-up in 2000, when 425 men had died, the frailty status of survivors (80.9%, n=1125, mean age 73 years) was assessed using a postal questionnaire including the RAND-36/SF-36 instrument. Phenotypic criteria were used to define frailty, and according to these criteria, 40.0% (n=450), 50.4% (n=567) and 9.6% (n=108) were classified as not frail, prefrail and frail, respectively. Risks are presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Compared with normal weight, the development of frailty was significantly higher among those men who were overweight or obese in midlife, with fully adjusted ORs (95% CI) of 2.06 (1.21-3.52) and 5.41 (1.94-15.1), respectively. Even the development of prefrailty was significantly increased with midlife overweight (OR 1.39; 95% CI, 1.03-1.87) and obesity (OR 2.96; 95% CI, 1.49-5.88). Age-adjusted composite CAD score in midlife predicted similarly 26-year total mortality (OR per 1% increase:1.16; 95% CI, 1.08-1.24) and development of frailty (OR 1.16; 95% CI, 1.02-1.33). CONCLUSION: Overweight/obesity and higher CAD risk in midlife were associated with frailty 26 years later. Preventing old age frailty should be recognized as an important goal of obesity and CVD risk control.

Chocolate, well-being and health among elderly men.

OBJECTIVE: We hypothesized that chocolate preference would be related to health and psychological well-being in old men. DESIGN, SETTING AND PARTICIPANTS: We have followed up a socio-economically homogenous group of men, born in 1919-1934, since the 1960s. In 2002-2003, a mailed questionnaire was used to assess the health and well-being (including questions related to positive life orientation, visual analogue scales and the Zung depression score) of survivors. In addition, candy preference was inquired. Those men who reported no candy consumption (n=108) were excluded from the analyses. OUTCOME MEASURES: Psychological well-being in old age. RESULTS: The response rate was 69% (1367 of 1991). Of the respondents, 860 and 399 preferred chocolate and other type of candy, respectively. The average age in both candy groups was 76 years. Of the respondents, 99% were home-dwelling, 96% were retired and 87% were presently married, without differences between the candy groups. Men preferring chocolate had lower body mass index and waist circumference, and they also reported more exercise and better subjective health (P=0.008) than other candy consumers. Variables related to psychological well-being were consistently better in those preferring chocolate. The differences were statistically significant in feeling of loneliness (P=0.01), feeling of happiness (P=0.01), having plans for the future (P=0.0002) and the Zung depression score (P=0.02). CONCLUSIONS: In this socioeconomically homogenous male cohort, chocolate preference in old age was associated with better health, optimism and better psychological well-being. SPONSORSHIP: The Academy of Finland, the Päivikki and Sakari Sohlberg Foundation, the Helsinki University Central Hospital and the Finnish Foundation for Cardiovascular Research.

Lercanidipine, enalapril and their combination in the treatment of elderly hypertensive patients: placebo-controlled, randomized, crossover study with four ABPM.

This double-blind, placebo-controlled, four-way balanced design crossover study included hypertensive patients aged 60-85 years with mean office-measured sitting systolic blood pressure (SBP) 160-179 mm Hg and daytime SBP > or =135 mm Hg. After a 2-week run-in period, during which previous medications were discontinued, each patient received the following four treatments in randomized order for 4 weeks each: lercanidipine 10 mg (L), enalapril 20 mg (E), lercanidipine 10 mg plus enalapril 20 mg (L/E) and placebo (P). At the end of each treatment period, office trough blood pressure (BP) was measured and a 24-h Ambulatory Blood Pressure Monitoring (ABPM) was performed. Seventy-five patients (mean age 66 years, office BP 168/92 mm Hg, daytime SBP 151 mm Hg) were randomized and 62 completed the study with four valid post-baseline ABPMs. The administration of P, L, E and L/E was associated with a mean 24-h SBP of 144, 137, 133 and 127 mm Hg, respectively. All active treatments significantly reduced the mean 24-h SBP in comparison with placebo, but L/E was significantly more effective than L and E alone. Similarly, office SBP was significantly more reduced with L/E (-16.9 mm Hg) than with L (-5.0 mm Hg) or E (-5.9 mm Hg). A BP <140/90 mm Hg was recorded in 18% of patients with L, 19% with E and 45% with L/E. Two patients on P and two on L/E were withdrawn from the study due to adverse events. In conclusion, combination therapy with L/E has additive antihypertensive effects on both ambulatory and office BP in elderly patients and is well tolerated.

A comparison of methods for estimating the transition:transversion ratio from DNA sequences.

Estimation of the ratio of the rates of transitions to transversions (TI:TV ratio) for a collection of aligned nucleotide sequences is important because it provides insight into the process of molecular evolution and because such estimates may be used to further model the evolutionary process for the sequences under consideration. In this paper, we compare several methods for estimating the TI:TV ratio, including the pairwise method [TREE 11 (1996) 158], a modification of the pairwise method due to Ina [J. Mol. Evol. 46 (1998) 521], a method based on parsimony (TREE 11 (1996) 158), a method due to Purvis and Bromham [J. Mol. Evol. 44 (1997) 112] that uses phylogenetically independent pairs of sequences, the maximum likelihood method, and a Bayesian method [Bioinformatics 17 (2001) 754]. We examine the performance of each estimator under several conditions using both simulated and real data.

Impact of midlife weight change on mortality and quality of life in old age. Prospective cohort study.

OBJECTIVE: To examine the effects of weight change during midlife on long-term mortality risk and quality of life in old age. DESIGN: Prospective cohort study with a 26-y follow-up. SUBJECTS: Socioeconomically homogeneous sample of 1657 men (born 1919-1934) who had attended health checks during the 1960s, were healthy and professionally active in 1974, and could recall their weight at the age of 25 y. MAIN OUTCOME MEASURES: Total mortality 1974-2000, scales of the RAND-36 (SF-36) health survey in 91% (n=1147) of the survivors in 2000. RESULTS: Body weight increased from 25 y of age until midlife, but not thereafter. During the 26-y follow-up, 392 men (23.7% of the initial 1974 cohort) died. Weight at 25 y of age did not predict death, but the adjusted mortality risk was significantly increased in the highest quartile of midlife weight gain (>/=15.0 kg) compared with lower quartiles (RR 1.39, 95% CI 1.12-1.73). In 2000, multivariate analyses (adjusted for body weight at the age of 25 y and in 2000, age, smoking, alcohol and subjective health and physical fitness in 1974) showed impairment in all eight RAND-36 scales (statistically significantly in seven) with increasing weight gain in midlife. CONCLUSION: In this homogeneous male cohort, only the largest weight gain from 25 y of age to midlife predicted long-term mortality. Weight gain sensitively affected later health-related quality of life, and zero weight gain up to midlife was associated with the best quality of life in old age.

Central and regional hemodynamics during acute hypovolemia and volume substitution in volunteers.

OBJECTIVES: To study the central and regional hemodynamics and oxygen consumption during acute hypovolemia and volume replacement with crystalloid and colloid solutions. DESIGN: Prospective, randomized, laboratory investigation. SETTING: Clinical physiology department at a university hospital. SUBJECTS: Eighteen healthy male volunteers, between 21 and 35 yrs of age (mean 26). INTERVENTIONS: Catheters were inserted in the cubital vein, brachial artery, pulmonary artery, thoracic aorta, right hepatic vein, and left renal vein for measurements of systemic arterial and pulmonary arterial pressures, total and central blood volumes, extravascular lung water, and the splanchnic (liver) and renal blood flow rates. The exchange of respiratory gases was measured, using the Douglas bag technique. Measurements were made before and after a venesection of 900 mL and again after the subjects had been randomized and received volume replacement with either 900 mL of Ringer's acetate solution 900 mL of albumin 5%, or 900 plus 900 mL of Ringer's solution. MEASUREMENTS AND MAIN RESULTS: Withdrawal of 900 mL of blood decreased cardiac output and the splanchnic and renal blood flow rates by between -16% and -20%. The oxygen uptake decreased by 13% in the whole body, while it remained unchanged in the liver and kidney. The systemic and pulmonary vascular resistances increased, while the extravascular lung water decreased. Autotransfusion of fluid from tissue to blood was indicated by hemodilution, which was most apparent in subjects showing only a minor change in peripheral resistance. Cardiac output, blood volume, and systemic vascular resistance were significantly more increased by infusion of 900 mL of albumin 5% than by 900 mL of Ringer's solution. However, infusion of 1800 mL of Ringer's solution increased the extravascular lung water and the pulmonary arterial pressures to significantly above baseline, while no significant difference from baseline was found after 900 mL of Ringer's acetate solution. CONCLUSIONS: Withdrawal of 900 mL of blood induces similar reductions in cardiac output as in the splanchnic and renal blood flow rates. A fluid shift from the extravascular to the intravascular fluid compartment might restore up to 50% of the blood loss. Optimal volume substitution with Ringer's solution can be effectuated by infusing between 100% and 200% of the amount of blood lost.

Haemodynamics during inhalation of a 50% nitrous-oxide-in-oxygen mixture with and without hypovolaemia.

BACKGROUND: Inhalation of a gas mixture containing 50% nitrous oxide in oxygen (N2O/O2) is widely used for pain relief in emergency situations, which may also be associated with blood loss. The aim of this study was to evaluate the haemodynamic effects of this gas mixture in normo- and hypovolaemic subjects. METHODS: Six healthy males were studied during inhalation of N2O/O2 before and after withdrawal of 900 ml of blood. On each occasion, we measured systemic and pulmonary arterial pressures, cardiac output, blood gases, extravascular lung water, and the blood flow and oxygen consumption in the whole body, liver and kidneys. RESULTS: Inhalation of N2O/O2 reduced the stroke volume and increased peripheral resistance. Oxygen uptake decreased in the liver (-30%) and in the whole body (-23%). Blood withdrawal reduced the pulmonary arterial and central venous pressures (-30 to -50%) and further decreased stroke volume and the blood flows to the liver and the kidney (-15%). The extravascular lung water tended to increase both during inhalation of N2O/O2 and during hypovolaemia. CONCLUSION: N2O/O2 aggravated the hypokinetic circulation induced by hypovolaemia. However, the oxygen consumption decreased only during inhalation of N2O/O2. This opens up the possibility that the cardiodepression associated with N2O/O2 is caused by a change in metabolic demands.

V/Q distribution and correlation to atelectasis in anesthetized paralyzed humans.

Regional ventilation and perfusion were studied in 10 anesthetized paralyzed supine patients by single-photon emission computerized tomography. Atelectasis was estimated from two transaxial computerized tomography scans. The ventilation-perfusion (V/Q) distribution was also evaluated by multiple inert gas elimination. While the patients were awake, inert gas V/Q ration was normal, and shunt did not exceed 1% in any patient. Computerized tomography showed no atelectasis. During anesthesia, shunt ranged from 0.4 to 12.2. Nine patients displayed atelectasis (0.6-7.2% of the intrathoracic area), and shunt correlated with the atelectasis (r = 0.91, P < 0.001). Shunt was located in dependent lung regions corresponding to the atelectatic area. There was considerable V/Q mismatch, with ventilation mainly of ventral lung regions and perfusion of dorsal regions. Little perfusion was seen in the most ventral parts (zone 1) of caudal (diaphragmatic) lung regions. In summary, shunt during anesthesia is due to atelectasis in dependent lung regions. The V/Q distributions differ from those shown earlier in awake subjects.

CT-assessment of dependent lung densities in man during general anaesthesia.

PURPOSE: We aimed to describe the frequency of atelectasis occurring during anaesthesia, to describe the size and pattern of the atelectasis, and to standardise the method of identifying the atelectasis and calculate its area. MATERIAL AND METHODS: Patients (n = 109) scheduled for elective abdominal surgery were examined with CT of the thorax during anaesthesia. RESULTS: In 95 patients (87%) dependent pulmonary densities were seen, interpreted as atelectasis. Two different types of atelectasis were found-homogeneous (78%) and non-homogeneous (9%). Attenuation values in histograms of the lung and atelectasis were studied using 2 methods of calculating the atelectatic area. CONCLUSION: On the basis of the present findings, we defined atelectasis as pulmonary dependent densities with attenuation values of -100 to +100 HU.

Phrenic nerve stimulation during halothane anesthesia. Effects of atelectasis.

BACKGROUND: Atelectasis formation during anesthesia may be due to loss of respiratory muscle tone, in particular that of the diaphragm. This was tested by tensing the diaphragm by phrenic nerve stimulation (PNS) and observing the effect on atelectasis. METHODS: Twelve patients (mean age 48 yr) without preexisting lung disease were studied during halothane anesthesia. PNS was executed with an external electrode on the right side of the neck. Chest dimensions and area of atelectasis were studied by computed tomography of the chest. RESULTS: Right-sided PNS against an occluded airway at functional residual capacity reduced the atelectatic area in the right lung from 5.1 to 3.8 cm2. The atelectasis was reduced to 1.1 cm2 after application of positive end-expiratory pressure (PEEP) of 10 cmH2O and large tidal volumes but increased to 2.5 cm2 within 1 min after discontinuation of PEEP. Commencement of PNS immediately after PEEP prevented the atelectasis from increasing, the mean area being 0.9 cm2. In seven patients, in whom the trachea was intubated with a double-lumen endobronchial catheter the atelectatic area was smaller during PNS with an open airway than during positive pressure inflation of the lung with the same volume as inspired during PNS (3.5 and 5.2 cm2, respectively. CONCLUSIONS: The findings indicate that contracting the diaphragm in the anesthetized subject reduces the size of atelectasis.

Chronic obstructive pulmonary disease and anaesthesia: formation of atelectasis and gas exchange impairment.

Gas exchange impairment and the development of atelectasis during enflurane anaesthesia were studied in 10 patients (mean age 70 yrs) with chronic obstructive pulmonary disease (COPD). Awake, no patient displayed atelectasis as assessed by computed X-ray tomography. The ventilation/perfusion distribution (VA/Q), studied by the multiple inert gas elimination technique, displayed an increased dispersion of VA/Q ratios (the logarithmic standard deviation of the perfusion distribution, mean log Q SD 0.99; upper 95% confidence limit of normal subject: 0.60), and increased perfusion of regions with low VA/Q ratios (0.005 less than VA/Q less than 0.1: 5.4% of cardiac output). Shunt was negligible (mean 0.6%). Computed chest tomography showed significantly larger cross-sectional thoracic areas than previously seen in subjects with healthy lungs (p less than 0.01). No atelectasis was seen in any patient. During anaesthesia there was a further worsening of the VA/Q mismatch with significantly increased log Q SD (1.29, p less than 0.05) but no increase in shunt (mean 1%). Minor atelectatic areas were noted in three patients, the others displayed no atelectasis at all. Chest dimensions were reduced by no more than 3% during anaesthesia, suggesting an unchanged or only minimally affected functional residual capacity. These findings contrast with those seen in patients with healthy lungs in whom atelectasis and shunt regularly develop during anaesthesia.

Atelectasis causes gas exchange impairment in the anaesthetised horse.

The anatomical basis of gas exchange impairment in the anaesthetised horse was studied by computerised tomography (CT; three shetland ponies) and morphological analysis (one pony and three horses). By means of CT, densities were seen in dependent lung regions early during anaesthesia, both with spontaneous breathing and with mechanical ventilation. The densities remained for some time where they had initially been created when the animal was turned from dorsal to sternal recumbency. Deep insufflation of the lungs reduced the dense area. Gas exchange was impaired roughly in proportion to the dense area. On histological analysis, the densities were atelectatic and congested with blood. Gravimetry showed no more extravascular water per unit lung tissue in the atelectatic than in the 'normal' regions, and the blood content was increased only slightly. It is concluded that the horse develops atelectasis in dependent lung regions early during anaesthesia in dorsal recumbency, and that atelectasis is the most likely explanation for the large shunt and impaired arterial oxygenation regularly seen during anaesthesia.

Ventilation-perfusion relationships and atelectasis formation in the supine and lateral positions during conventional mechanical and differential ventilation.

Patients without respiratory symptoms were studied awake and during general anesthesia with mechanical ventilation prior to elective surgery. Ventilation-perfusion (VA/Q) relationships, gas exchange and atelectasis formation were studied during five different conditions: 1) supine, awake; 2) supine during anesthesia with conventional mechanical ventilation (CV); 3) in the left lateral position during CV; 4) as 3) but with 10 cm of positive end-expiratory pressure (PEEP) and 5) as 3) but using differential ventilation with selective PEEP (DV + SPEEP) to the dependent lung. Atelectatic areas and increases of shunt blood flow and blood flow to regions with low VA/Q ratios appeared after induction of anesthesia and CV. With the patients in the lateral position, further VA/Q mismatch with a fall in PaO2 and increased dead space ventilation was observed. Atelectatic lung areas were still present, although the total atelectatic area was slightly decreased. Some of the effects caused by the lateral position could be counteracted by adding PEEP. Perfusion of regions with low VA/Q ratios and venous admixture were then diminished, while PaO2 was slightly increased; shunt blood flow and dead space ventilation were essentially unchanged. During CV + PEEP, there was a decrease in cardiac output, compared to CV in the lateral position. DV + SPEEP was more effective than CV + PEEP in decreasing shunt flow and increasing PaO2 in the lateral position; in addition to this, cardiac output was not affected.

The influence of body position and differential ventilation on lung dimensions and atelectasis formation in anaesthetized man.

The effects of body position and anaesthesia with mechanical ventilation on thoracic dimensions and atelectasis formation were studied by means of computerized tomography in 14 patients. Induction of anaesthesia in the supine position reduced the cross-sectional area for both lungs and caused atelectasis formation in dependent lung regions in 4/5 patients. Conventional ventilation with positive end-expiratory pressure (PEEP) increased thoracic dimensions and reduced, but did not eliminate, the atelectatic areas. The vertical diameters of both lungs were smaller in the lateral position as compared to the supine position (16.7 vs 10.4 cm in the left lung and 17.3 vs 12.8 cm in the right lung). The lateral positioning also caused a large reduction of the atelectatic area in the non-dependent lung. Differential ventilation with selective PEEP to the dependent lung eliminated (3/8 patients) or reduced (5/8 patients) dependent lung atelectasis. It can be concluded that lung geometry is altered in the lateral position: the shape of the lung makes the vertical diameter of each lung less in the lateral position, compared to the supine position. The atelectatic areas are mainly located in the dependent lung in the lateral position, and these atelectatic areas could be further reduced by selective PEEP to this lung.

Atelectasis and gas exchange impairment during enflurane/nitrous oxide anaesthesia.

The development of atelectasis and effects on gas exchange during enflurane anaesthesia in nitrogen/oxygen or nitrous oxide/oxygen (inspired oxygen fraction 0.4) were studied in 16 lung-healthy patients (mean age 49 years). Awake, no subject displayed atelectasis as assessed by computed x-ray tomography of the thorax. Pulmonary gas exchange, studied by multiple inert gas elimination technique, and blood gases were normal. After 10 min of enflurane anaesthesia in nitrogen/oxygen, 14 of 16 subjects had developed atelectasis. After 30 min of enflurane anaesthesia in nitrogen/oxygen or nitrous oxide/oxygen, all patients had developed atelectasis, and a further increase was observed after 90 min of anaesthesia to approximately 5% of the intrathoracic area. There was no difference between the two anaesthesia groups. In the nitrogen group, shunt rose to a maximum of 5.8% at 30 min of enflurane anaesthesia, with a significant reduction to the initial anaesthesia level after 90 min of anaesthesia (3.4%). Perfusion of poorly ventilated lung regions (low VA/Q) averaged 4-5% and did not vary significantly during the anaesthesia. In the nitrous oxide group, shunt increased to 6.3% after 90 min of anaesthesia, and there was a parallel decrease in perfusion of low VA/Q regions. The findings suggest that besides prompt collapse of lung tissue during induction of anaesthesia, absorption of gas from closed-off or poorly ventilated regions takes place and further increases the atelectatic area.

Pulmonary densities during anaesthesia. An experimental study on lung morphology and gas exchange.

The nature of dense areas in dependent lung regions regularly seen in anaesthetized humans was examined in a sheep model. During anaesthesia with muscle paralysis and mechanical ventilation dense areas in dependent lung regions could be seen by means of computerized tomography (CT). They had the same location and the same attenuation as in anaesthetized humans. Gas exchange impairment tended to increase in proportion to the size of the dense area on the CT scan. Microscopy showed that the densities in the sheep were atelectatic lung regions, with no or little interstitial oedema and only minor vascular congestion. The atelectatic lung tissue was sharply demarcated and the lung tissue in the immediate vicinity was well aerated, or even hyperinflated. Gravimetry showed the same amount of extravascular fluid and blood per unit lung weight in the atelectatic lung and in the aerated lung region. It is concluded that the densities appearing in dependent lung regions during anaesthesia are caused by atelectasis.

Thoracoabdominal restriction in supine men: CT and lung function measurements.

Thoracoabdominal restriction was brought on by means of a corset, and the subsequent effects on thoracic dimensions and lung tissue were studied by computerized tomography (CT) and by various lung function tests in supine healthy volunteers (mean age 30 yr). Restriction caused reductions in total lung capacity (helium equilibration) from mean 6.84 to 4.80 liters, in functional residual capacity (FRC) from 2.65 to 2.08 liters, and in vital capacity from 5.16 to 3.45 liters. Closing capacity (single-breath N2 washout) fell from 2.42 to 1.88 liters, thus matching the reduction in FRC. The static pressure-lung volume curve was shifted to the right by 1.5 cmH2O at 50% of total lung capacity. However, no change in the slope of the curve was observed. The diaphragm was moved cranially by 1.2 cm, and the thoracic cross-sectional area was reduced by a mean 32 cm2 at a level just above the diaphragm. No changes in the lung tissue were seen on CT scanning. Gas exchange, as assessed by multiple inert gas elimination technique and arterial blood gas analysis, was unaffected by restriction. It is concluded that in supine subjects, thoracoabdominal restriction that reduces FRC by 0.6 liter is not accompanied by atelectasis (normal CT scan). In this respect the result differs from that found in anesthetized supine subjects who show the same fall in FRC and atelectasis in dependent lung regions.

Computerized tomography of the chest and gas exchange measurements during ketamine anaesthesia.

The effects of atelectasis on pulmonary gas exchange were studied in eight supine, clinically lung-healthy patients. Atelectasis was studied by computerized tomography (CT), and gas exchange by blood gas analysis. The distribution of ventilation/perfusion ratios was assessed by a multiple inert gas elimination technique. No patient had any signs of atelectasis in the awake state, and gas exchange was normal. During ketamine anaesthesia and spontaneous breathing, lung ventilation and perfusion were well matched in most subjects. In one patient there was perfusion of poorly ventilated regions amounting to 14% of cardiac output, and in another there was a shunt of 4% of cardiac output; this patient was the only one who developed atelectasis in dependent lung regions. After muscular relaxation and commencement of mechanical ventilation, all patients but one developed both shunt (2-6% of cardiac output) and atelectasis. The shunt correlated to the size of atelectasis. It is concluded that the occurrence of shunt during anaesthesia is related to the development of atelectasis in dependent lung region, which is consistent with the hypothesis that it is changes in chest-wall mechanics that cause atelectasis.

Postoperative analgesia with intrapleural administration of bupivacaine-adrenaline.

Twenty-one patients who underwent elective cholecystectomy were studied with regard to the effect of intrapleural administration of bupivacaine-adrenaline solution on postoperative pain and ventilatory capacity. Administration of 10 or 20 ml of 2.5 mg/ml or 5 mg/ml bupivacaine solution resulted in complete analgesia in 143 of 159 administrations. Most patients experienced the maximal pain-relieving effect within 1-2 min and analgesia persisted as a rule for 3-5 h. Forced vital capacity and forced expiratory volume in 1 s increased after intrapleural analgesia on average by 56% and 46%, respectively, on the first postoperative day and by 35% and 51%, respectively, on the second day. There was no significant difference in the analgesic effect or in the effect on the ventilatory capacity between the 2.5 mg/ml or the 5 mg/ml solution, in either the 10 ml or the 20 ml dose. Placebo (NaCl) given intrapleurally had no effect on pain or on the ventilatory capacity. The plasma concentration of bupivacaine after intrapleural administration showed a wide interindividual variation, with considerably higher average values when the 5 mg/ml solution had been used than for the 2.5 mg/ml solution. Although no toxic effects were noted, a 2.5 mg/ml solution, which can be given in an initial dose of 20 ml and top-up doses of 10 ml at 3-6 h intervals, is recommended. In four patients minor pneumothorax developed when the catheter was introduced. The pneumothorax was easily evacuated, but underlines the need for great care when introducing the catheter.