RESUMO
AIM: For previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). METHODS: From the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. RESULTS: All 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1 years. The mean (SD) annual treatment costs ( per kg) were 4391 (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383 448 (259 085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. CONCLUSIONS: Early high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2 years.
Assuntos
Hemofilia A/tratamento farmacológico , Hemofilia A/economia , Adolescente , Criança , Pré-Escolar , Documentação , Fator VIII/economia , Fator VIII/imunologia , Fator VIII/uso terapêutico , Feminino , Finlândia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hemofilia A/imunologia , Humanos , Tolerância Imunológica , Lactente , Recém-Nascido , Masculino , Resultado do TratamentoRESUMO
INTRODUCTION: Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. AIM: This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C < 0.01 IU mL(-1) ). METHODS: We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. RESULTS: Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median age of 11.4 months, 90% via a central venous access device. The initial product was rFVIII in 63% and pd-FVIII in 37%, moreover in 24% pd-FVIII was switched to rFVIII concentrate during the 75 EDs. Non-transient inhibitors developed in 9/51 (17.6%; 13.7% high titre) children with primary and in 4/11 (36.4%; 27.3% high titre) patients with secondary prophylaxis (P = 0.24). Overall, 74% had a high-risk genotype similarly distributed among the prophylaxis groups. The history of a major bleed enhanced ID (aHR, 4.0; 95% CI, 1.2-13.7), whereas FVIII treatment intensity or source and early implantation of ports did not increase ID risk. CONCLUSION: The cumulative incidence of ID was low notwithstanding prevalent high-risk mutations. Despite patient-related risk factors, our management involving early intensive primary prophylaxis via ports helps to prevent bleeds and lower the incidence of inhibitors.
Assuntos
Anticorpos Neutralizantes/sangue , Coagulantes/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Pré-Escolar , Fator VIII/genética , Finlândia , Genótipo , Hemofilia A/genética , Hemofilia A/patologia , Hemorragia , Humanos , Lactente , Recém-Nascido , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Children with haemophilia require venous access for regular infusion of coagulation factors. A central venous access device (CVAD) ensures long-term access but associates with infectious and non-infectious complications with proposed risk factors of young age at initial CVAD implantation and presence of an inhibitor. Our aim was to evaluate the incidence and risk factors for complications associated with CVAD usage in a retrospective nationwide multicentre study in five Finnish Paediatric Haemophilia Treatment Centers. Our study investigated 106 CVADs in 58 patients with 137 971 CVAD days. The median access survival was 1159 CVAD days, and most often a malfunction led to CVAD removal after a long survival (median of 1640 CVAD days). We detected a very low bloodstream infection rate (0.12/1000 CVAD days). The presence of neutralizing inhibitor was a significant risk factor for infection. Heparin vs. saline flushing did not influence the CVAD outcome. We detected a lower infection rate than previously reported, although 90% of the patients were very young (<2 years) at first insertion (median age = 1.02 year). Port access was frequent after initial implantation: six patients (10%) used the port daily for immune tolerance induction therapy and 74% at least twice weekly for prophylaxis. Young age did not increase the risk of infections, as 59% of the CVAD-related infections were recorded in children over 6 years of age. Our national experience confirms the safety of prophylactic factor concentrate administration via ports even in very young children.
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Cateterismo Venoso Central/efeitos adversos , Hemofilia A/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Finlândia , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Improvements in cancer therapy have resulted in an expanding population of early-onset cancer survivors. In contrast to childhood and adolescent cancer survivors, there is still a lack of data concerning late morbidities among young adult (YA) cancer survivors. Thus, our aim was to investigate cardiac and vascular morbidity among early-onset cancer survivors with a special interest in YA cancer survivors. In a population-based setting, we explored the risk of cardiovascular disease in early-onset cancer survivors compared to healthy siblings. Patients diagnosed with cancer below 35 years of age since 1975 were identified from the Finnish Cancer Registry, and 5-year survivors were included in our study (N = 13,860). Information on cardiovascular morbidity was collected from the national hospital discharge registry. Compared to siblings, cancer survivors aged 0-19 and 20-34 at diagnosis had significantly elevated hazard ratios (HRs) for the studied outcomes: HR 13.5 (95% CI 8.9-20.4) and 3.6 (95% CI 2.8-4.6) for cardiomyopathy/cardiac insufficiency; HR 3.4 (95% CI 2.3-5.1) and 1.7 (95% CI 1.4-2.0) for atherosclerosis/brain vascular thrombosis; HR 3.3 (95% CI 1.7-6.5) and 1.8 (95% CI 1.5-2.1) for myocardial infarction/cardiac ischemia and HR 1.7 (95% CI 1.2-2.6) and 1.4 (95% CI 1.2-1.7) for cardiac arrhythmia. In both groups, depending on the outcome, the HR for adverse events was highest among lymphoma, brain tumor, leukemia and testicular malignancy survivors. Our results regarding late effects of childhood cancer survivors confirmed previous findings. Additionally, our study provides novel information concerning the YA cancer survivor population. Hence, our data may help in planning the risk-based long-term follow-up of early-onset cancer survivors.
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Doenças Cardiovasculares/complicações , Neoplasias/complicações , Taxa de Sobrevida , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Finlândia , Humanos , Lactente , Recém-Nascido , Irmãos , Adulto JovemRESUMO
The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media. Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis. Rhinovirus (24%) and respiratory syncytial virus (13%) were the two most common viruses detected. Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently. The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media. Ninety-four percent of the children had symptoms of upper respiratory tract infection. Fever was reported in 55% and earache in 47% of cases. Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients. No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis. Most patients respond well to antimicrobial therapy despite the coexisting viral infection. If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients.
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Otite Média/etiologia , Infecções Respiratórias/complicações , Viroses/complicações , Doença Aguda , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Moraxella catarrhalis/isolamento & purificação , Otite Média/microbiologia , Estudos Prospectivos , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/microbiologia , Rhinovirus/isolamento & purificaçãoRESUMO
The hemodynamic effects of intravenous labetalol (a combined alpha- and beta-blocking agent) were studied in 11 patients during early post-open heart surgery hypertension. With a mean dosage of 15 mg, labetalol reduced both systemic arterial pressures and the heart rate by an average of 21 percent (p < .001). The patients failed to compensate for the decline in pressure and pulse rate by elevation of their stroke volume, and even the cardiac index (CI) was severely depressed (from 2.30 to 1.67 L/min/m2, ie, 27 percent; p < .001). Neither left ventricular filling pressure nor vascular resistance was affected by labetalol early after open heart surgery. In four patients, 3 mg of glucagon after administration of labetalol elevated pulmonary arterial pressures and increased the CI by 16 percent. Two patients were observed on the preoperative day, and their response to labetalol was similar to that described in earlier studies: during blood pressure decline, CI was slightly augmented, and the systemic vascular resistance was greatly reduced (26 percent). The results indicate that after open heart surgery, patients are highly sensitive to the beta-blocking effects of labetalol, and although labetalol can greatly reduce myocardial oxygen consumption, it cannot be recommended for the treatment of post-open heart surgery hypertension.
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Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Etanolaminas/administração & dosagem , Glucagon/farmacologia , Hemodinâmica/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Labetalol/administração & dosagem , Adulto , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Ensaios Clínicos como Assunto , Depressão Química , Feminino , Glucagon/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/etiologia , Injeções Intravenosas , Período Intraoperatório , Labetalol/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Resistência Vascular/efeitos dos fármacosRESUMO
To evaluate the occurrence and clinical significance of respiratory virus infections in children during anticancer treatment, we studied 75 consecutive episodes of febrile infection in 32 children during 17 months. Viral antigen detection for 7 respiratory viruses, viral culture for rhinoviruses and enzyme immunoassay serology were used. Evidence for respiratory virus infection was found in 28 (37%) cases. Rhinovirus was the most common virus detected in 13 (17%) episodes. The other etiologic agents were respiratory syncytial virus (6 episodes), parainfluenza virus type 3 (5 episodes), adenovirus (4 episodes), influenza A virus (3 episodes), and influenza B virus (1 episode). Respiratory virus infections were diagnosed as often in leukopenic as in non-leukopenic patients (37% vs. 38%). In 4 cases bacteremic infection was diagnosed. We found no difference in serum C-reactive protein values when episodes positive for respiratory viruses were compared with virus-negative episodes. Our observations show that respiratory virus infections are common in febrile children receiving anticancer treatment. Diagnostic tests for respiratory viruses should be used more often in evaluation of fever in these patients.
Assuntos
Hospedeiro Imunocomprometido , Neoplasias/complicações , Infecções Respiratórias/complicações , Viroses/complicações , Adolescente , Antineoplásicos/uso terapêutico , Proteína C-Reativa/análise , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Febre de Causa Desconhecida/etiologia , Febre de Causa Desconhecida/virologia , Humanos , Lactente , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/virologia , Prognóstico , Estudos Prospectivos , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologia , Viroses/diagnóstico , Viroses/imunologiaRESUMO
We studied the association of acute otitis media with different respiratory virus infections in a pediatric department on the basis of epidemics between 1980 and 1985. Altogether 4524 cases of acute otitis media were diagnosed. The diagnosis was confirmed by tympanocentesis in 3332 ears. Respiratory virus infection was diagnosed during the same period in 989 patients by detecting viral antigen in nasopharyngeal mucus. There was a significant correlation between acute otitis media and respiratory virus epidemics, especially respiratory syncytial virus epidemics. There was no significant correlation between outbreaks of other respiratory viruses and acute otitis media. Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media. In this study on hospitalized children Haemophilus influenzae strains were the most common bacteriologic pathogens in middle ear fluid, occurring in 19% of cases. Streptococcus pneumoniae was present in 16% and Branhamella catarrhalis in 7% of cases. There was no association between specific viruses and bacteria observed in this study.
Assuntos
Otite Média/complicações , Infecções Respiratórias/complicações , Feminino , Finlândia , Haemophilus influenzae/isolamento & purificação , Humanos , Masculino , Moraxella catarrhalis/isolamento & purificação , Muco/microbiologia , Nasofaringe/microbiologia , Otite Média/epidemiologia , Otite Média/microbiologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções por Respirovirus/complicações , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
We studied rhinovirus in the middle ear fluid of 61 children with subacute or chronic otitis media with effusion. Rhinovirus was recovered from the middle ear fluid of 5 children with subacute otitis media with effusion. The minimum duration of effusion was 32 to 60 days. Additionally, 1 patient had middle ear fluid that was positive for adenovirus. Bacterial pathogens were cultured from the middle ear fluid of 20 of 61 patients. Our finding that rhinovirus can be isolated from middle ear fluid after an asymptomatic period of several weeks suggests its possible role in the development of otitis media with effusion.
Assuntos
Otite Média com Derrame/microbiologia , Rhinovirus/isolamento & purificação , Bactérias/isolamento & purificação , Criança , Pré-Escolar , Doença Crônica , Orelha Média/microbiologia , Feminino , Humanos , Lactente , MasculinoRESUMO
Gas-chromatographically determined serum concentrations of midazolam were recorded before, during and after cardiopulmonary bypass in patients scheduled for a coronary artery bypass grafting operation. Following single 0.075 mg/kg (n = 6) and 0.15 mg/kg (n = 6) intravenous injections of midazolam, a mean distribution phase half-life of 3.4 and 4.4 min respectively was calculated. At the establishment of the bypass, a rapid drop in the concentration of midazolam was observed followed by a significant increase in concentration during the postperfusion period. The apparent mean elimination phase half-life (281 min) of midazolam was longer than that (about 120 min) measured in earlier works in young, healthy subjects. Thus the metabolism of midazolam during the postperfusion period appears to be slower.
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Benzodiazepinas/metabolismo , Ponte Cardiopulmonar , Hipnóticos e Sedativos/metabolismo , Benzodiazepinas/sangue , Meia-Vida , Humanos , Hipnóticos e Sedativos/sangue , Cinética , Masculino , Midazolam , Pessoa de Meia-Idade , Distribuição Aleatória , Fatores de TempoAssuntos
Genes ras , Leucemia Mieloide/genética , Mutação , Sequência de Bases , DNA de Neoplasias/genética , Humanos , LactenteAssuntos
Hipotermia , Adulto , Eletrocardiografia , Humanos , Hipotermia/complicações , Hipotermia/fisiopatologia , Masculino , TemperaturaRESUMO
AIM: Twenty-five male patients were investigated to elucidate the correlation of semen parameters and other related parameters in the assessment of spermatogenesis after childhood cancer treatment. METHODS: Evaluation of given cancer treatment, anthropometric and testicular size measurements, semen analysis, and measurement of gonadotrophins, testosterone, sex hormone-binding globulin (SHBG), and inhibin B were performed according to a protocol. RESULTS: Median (range) sperm concentration (SC) was 35.5 (0-273)x10(6)/mL, and percentage of motile sperm 56 (0-86)%. Testicular size (r=0.73, p<0.001) and the level of inhibin B (r=0.66, p<0.001) correlated strongly to SC. SC correlated negatively to FSH (r=0.46, p=0.03). Only testicular size predicted SC significantly (p=0.03). Inhibin B showed highest area under ROC curve (0.83, 95%CI 0.67-0.99) in showing SC<20x10(6)/mL. Body mass index (BMI) did not correlate with SC, but negative correlation between BMI and SHBG was found (r=-0.41, p=0.04). CONCLUSION: Although semen analysis is a useful instrument for fertility assessment in men, it is often difficult to get these samples from childhood cancer survivors. Thus, indirect methods are needed in prediction of possible sperm count impairment in postpubertal adolescents after cancer treatment. When combined with the data on testicular size and follicle-stimulating hormone (FSH) level, inhibin B gives valuable addition to the estimations of spermatogenesis.
Assuntos
Fertilidade , Neoplasias/terapia , Espermatogênese , Adolescente , Adulto , Criança , Pré-Escolar , Hormônio Foliculoestimulante/sangue , Seguimentos , Humanos , Lactente , Inibinas/sangue , Masculino , Espermatogênese/efeitos dos fármacos , Espermatogênese/efeitos da radiação , Testículo/anatomia & histologia , Testículo/diagnóstico por imagem , Testosterona/sangue , UltrassonografiaRESUMO
Pearson syndrome is a rare multiorgan mitochondrial disorder that causes substantial disability and usually leads to premature death. We describe an infant with Pearson syndrome who showed, in addition to the typical features of the syndrome, cleft lip and palate and hypospadias.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Hipospadia/genética , Doenças Mitocondriais/genética , Anormalidades Múltiplas/genética , Fenda Labial/complicações , Fissura Palatina/complicações , DNA Mitocondrial/metabolismo , Deleção de Genes , Humanos , Hipospadia/complicações , Lactente , Masculino , Erros Inatos do Metabolismo/metabolismo , Doenças Mitocondriais/complicações , Transtornos Psicomotores/complicações , Transtornos Psicomotores/genética , SíndromeRESUMO
The records of 794 tracheostomized patients were studied in order to discover complication associated with tracheostomy. Bacterial colonization was found in 92% of patients from whom tracheal secretions were cultured, crusted airways in 5%, tracheobronchitis is 16%, pneumonia in 22% and tracheobronchial bleeding in 22% of patients in the form of bloody secretions. Tracheo-arterial erosion with massive bleeding was confirmed in five patients and treatment was successful in one case only. Tracheo-oesophageal fistula was diagnosed in three patients at autopsy. After extubation, symptomatic tracheal stenosis developed in nine patients, two of whom died. The overall mortality rate was 46% reflecting the seriousness of patients' diseases. Tracheostomy related mortality rate was 1.4%. The study was divided into two periods, one before the introduction of an intensive care unit (ICU) and the second thereafter when most of the patients were treated in ICU. The total number of complications during tracheostomy operation was higher during the first period than that in the second period. During tracheostomy treatment, crusted airways were confirmed more often during the first period whereas tracheobronchitis was observed more frequently during the second period. In other respects the incidence of separate complications did not differ statistically. The total number of complications increased but the incidence of separate complications did not increase, although there was a greater number of patients who were tracheostomized or received respirator treatment for a long period.
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Traqueotomia/efeitos adversos , Adolescente , Adulto , Idoso , Obstrução das Vias Respiratórias/etiologia , Bronquite/etiologia , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/etiologia , Pneumotórax/etiologia , Atelectasia Pulmonar/etiologia , Estudos Retrospectivos , Doenças da Traqueia/etiologia , Traqueíte/etiologia , Traqueotomia/mortalidadeRESUMO
We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy. The mean duration of preenrollment antimicrobial therapy was 4.8 days. For comparison we studied 66 children with newly diagnosed acute otitis media. Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05). Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group. Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy. All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection. Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection. Resistant bacteria seem to be a less common cause of failure of the initial treatment.
Assuntos
Otite Média com Derrame/etiologia , Infecções por Respirovirus , Doença Aguda , Adolescente , Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Nasofaringe/microbiologia , Otite Média com Derrame/tratamento farmacológico , Otite Média com Derrame/microbiologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções por Respirovirus/microbiologiaRESUMO
The tracheas of 37 tracheostomized patients (31 men and 6 women) were studied in connection with obduction. Twenty-six patients had been intubated before tracheostomy and 29 of the tracheostomized patients were treated with a respirator. At autopsy, the damage caused to the tracheal wall by the cuff was studied macroscopically; the finding was photographed for later investigation and samples were taken from the damaged area for microscopic examination. The purpose of the study was to determine the damage caused to the tracheal wall by the low-volume cuff we have used during the last 4 years. The cuff diameter was nearly the same as that of the trachea. The injuries were grouped according to their extent and depth as mild, moderate or severe, and the groups contained, respectively, 5, 12 and 20 patients. It seemed that cuff pressure played a greater part in causing damage than the duration of cuff strain. Factors in the clinical condition of patients, like hypotension, uraemia, respiratory infections, sepsis and use of steroids, may have had an effect on the development of damage. The injuries caused by the cuff used are so severe that there is every reason to use instead the low-pressure, high-volume cuff, which has been shown to cause less damage, whenever long-term treatment is involved.
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Intubação Intratraqueal/efeitos adversos , Traqueia/lesões , Traqueotomia/efeitos adversos , Adolescente , Adulto , Idoso , Cartilagem/lesões , Cartilagem/patologia , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Traqueia/patologiaRESUMO
Changes in central and coronary haemodynamics and myocardial oxygenation during anaesthesia induction, intubation, skin incision and sternotomy were studied in 24 patients undergoing a coronary artery bypass grafting operation under either high-dose fentanyl or enflurane anaesthesia. The anaesthesia induction caused no changes in the coronary haemodynamics in either group, in spite of a marked decrease in the coronary perfusion pressure during enflurane induction. In both groups a decrease in the coronary sinus blood flow and an increase in the coronary vascular resistance was observed after the intubation. At this stage, two patients in both groups had a low level of myocardial lactate extraction, indicating possible myocardial ischaemia; mean myocardial lactate extraction had decreased significantly from the awake level in both groups. A circulatory response to surgical stimulation was seen in both groups, although it could be somewhat better controlled during enflurane anaesthesia. In the enflurane patients the increase in myocardial oxygen demand was accompanied by increased coronary flow, while in the fentanyl group the increase in coronary flow was not in proportion to the increased oxygen demand, and an increase in myocardial oxygen extraction was also seen. During surgery, three fentanyl patients and one enflurane patient had a low level of myocardial lactate extraction.