Effects of age on circadian blood pressure and heart rate rhythms in patients with primary hypertension.

To evaluate whether circadian rhythms in blood pressure and heart rate are influenced by age, we analyzed 24-h ambulatory blood pressure and heart rate recordings from 31 patients with primary hypertension. Data were collected during hospitalization, after a drug-free run-in period. Set times were administered for lights-on, meals, and lights-off. Daytime napping was prohibited. The patients were divided into sex-matched groups of young (group I: 25-45 years, n = 9), middle-aged (group II: 47-57 years, n = 11), and old (group III: 57-74 years, n = 11) subjects. Hourly data were analysed by fitting a two-component cosine function (24- and 12-h periods). Amplitudes of the circadian rhythms in systolic blood pressure and heart rate were significantly reduced with age. This finding could be partly attributed to the recording of higher nocturnal values in older patients. Elderly hypertensives also evidenced a significantly greater ultradian component (12-h period) in the systolic blood pressure rhythm than did young patients, with the secondary afternoon decline in blood pressure being more pronounced in groups II and III. The 24-h acrophase of heart rate was found to occur approximately 1.6 h earlier than that of systolic blood pressure in the young group (p < 0.01). This phase advance of heart rate compared with systolic blood pressure was reduced to 1 h in group II (p < 0.05) and was not evident in group III (p > 0.1). These results indicate that circadian blood pressure and heart rate profiles of primary hypertensives change with age. Since measures were obtained in a typical clinical setting, these findings have implications for the diagnosis and treatment of hypertension in the elderly. The marked afternoon decline in blood pressure for the elderly patients may also render conventional cosinor analysis inappropriate for accurate description of the circadian rhythms of geriatric hypertensives.

[Anesthesia for surgery in ambulatory patients: organizational aspects of the hospital physician]. / Anästhesie für Operationen bei ambulanten Patienten: Organisatorische Aspekte des Krankenhausarztes.

At first sight it seems impossible to put into practice the 1992 resolution of the German Federal Council recommending increased frequency of hospital based operative care for ambulatory patients and the duty to do so under full financial coverage. A detailed analysis of the current situation suggests that this may be possible even today--with some reservations regarding the infrastructure of the hospitals. Selection and preparation of the patient is a process in which the anaesthesiologist must play an important role. Delegation of this duty to the surgeon or the general practitioner is not permitted. The anaesthesiologist must have sufficient time, prior to the procedure, to meet the patient; meeting the patient for the first time a few minutes before induction of anaesthesia is unacceptable. Even if one concedes freedom of methods, one drug and one procedure should be avoided while caring for surgical ambulatory patients: this drug is succinylcholine, because of life-threatening hyperkaliaemia in children with occult myopathy and severe and frequent myalgia especially in ambulatory patients. The procedure not suitable in ambulatory patients is subarachnoidal analgesia--due to an unacceptably high percentage of headaches in young ambulatory patients. The postoperative care and observation must be delegated to especially qualified persons only--and these persons should not be distracted by duties outside the recovery area. The anaesthetist must--in addition--be available at all times without delay. Pain, nausea and emesis molest the ambulatory patient during the postoperative course to a particular extent. The anaesthesiologist must take care of these complaints--even if the patient is discharged.(ABSTRACT TRUNCATED AT 250 WORDS)

[Heart arrest in children after intravenous injection of succinylcholine in the ENT operating room]. / Herzstillstand bei Kindern nach intravenöser Injektion von Succinylcholin im HNO-Operationssaal.

Acute rhabdomyolysis with hyperkalemia has been followed by ventricular dysrhythmia, cardiac arrest and death after the administration of succinylcholine to apparently healthy children who were subsequently found to have undiagnosed skeletal muscle myopathies. Boys have mostly been affected. Reports of anesthesia emergencies from the United States and Germany have indicated that serious side effects of succinylcholine are not as rare as previously thought. This disorder often presents as sudden cardiac arrest within minutes after the administration of the drug. The tragedy is that an apparently healthy child dies abruptly during what was considered to be a relatively uncomplicated surgical procedure (most often in ENT surgery). Due to the abrupt onset of rhabdomyolysis, routine resuscitative measures are likely to be unsuccessful. Extraordinary measures (including institution of extracorporeal circulation) and prolonged efforts have resulted in successful resuscitation of some cases. Since there are usually no signs or symptoms to alert the practitioner to patients at risk, the use of succinylcholine in children should be reserved for emergency intubations or instances in which immediate securing of the airway is necessary.

["Round the clock"--an information service for malignant hyperthermia emergencies]. / "Rund um die Uhr"--Informationsdienst für maligne Hyperthermie-Notfälle.

A 24-hour 7-day telephone service has been created for emergency consultation: MH-hotline 030/3035504 (daytime) or 030/30351 (after office hours). In emergencies callers should ask for a consultant, indicating the code word "malignant hyperthermia" and give their name, the name of the institution and the telephone number.

[New findings and experiences in the field of malignant hyperthermia]. / Neue Erkenntnisse und Erfahrungen auf dem Gebiet der malignen Hyperthermie.

New publications on malignant hyperthermia (MH), with direct clinical importance, are reported. Since even in the recent past patients have died from MH in spite of therapy with dantrolene, the effectiveness of dantrolene is discussed in particular. Atypical clinical pictures of MH are presented. Special psychiatric syndromes (malignant neuroleptic syndrome and acute febrile catatonia), rhabdomyolysis with myoglobinuria following strenuous exercise or exposure to heat are mentioned, as these disorders appear to be related to MH, in that they are hypermetabolic syndromes implying a muscle membrane dysfunction. The role of slow calcium channel blockers and 5-hydroxytryptamine antagonists as prophylactic or therapeutic agents in MH is discussed. A schedule describing how to diagnose, treat and prevent MH, considering recent advances, is presented.

[Reasons for the persistent lethality of malignant hyperthermia and recommendations for its reduction]. / Gründe für die persistierende Letalität der Malignen Hyperthermie und Empfehlungen zu deren Senkung.

Dantrolene is the only known specific treatment of malignant hyperthermia (MH). Following official approval an intravenous formulation of dantrolene became clinically available for emergency treatment of MH. At that time it had been anticipated, that with dantrolene therapy combined with constant vigilance each case of MH could be treated successfully and the mortality rate should be close to zero. Surprisingly enough, reports of death due to MH continue to be published up to the present. Analysis of case reports revealed the following reasons for the discrepancy between the expectations and the clinical reality: 1. Delay in early diagnosis due to preoccupation with the name-giving symptom hyperthermia: lack of MH-sensitive monitoring (i.e. capnometry, pulse oximetry, blood gas analysis). 2. Preoccupation with non specific facets of therapy: measures such as cooling, change of the anaesthesia machine, transfer of the patient to the intensive care unit or the administration of drugs which have been shown to be ineffective in treating MH may not only be a waste of time, but fully disregard the prime factor in therapy--intravenous administration of dantrolene. 3. Administration of an insufficient amount of dantrolene and delayed start of specific therapy due to failure to have immediate access to intravenous dantrolene. 4. Failure to increase minute ventilation immediately after making the diagnosis to meet elevated metabolic demands. A recommendation is presented how to diagnose, to treat and prevent MH, considering present day diagnostic and therapeutic measures in the presence of the presumptive diagnosis of MH.

[Malignant hyperthermia]. / Die maligne Hyperthermie.

Malignant hyperthermia (MH) is a rare syndrome seen when susceptible individuals are exposed to one or more of various triggering agents, most commonly a depolarizing muscle relaxant or an inhalational anaesthetic agent. There is a dramatic rise in metabolic rate and oxygen consumption which if not treated promptly and effectively results, in the majority of cases, in the patient's death. Fatal responses to physical stress associated with the familial muscular disease known as MH are being increasingly reported in situations not related to anaesthesia or drugs. Moreover, cases of MH were recognized to be "induced" in the postoperative period when obviously the major effects of anaesthesia were no longer of important consideration. Therefore a more expanded concept of MH seems to develop, including the assumption that one of the other factors in MH is stress. The implication of this extends far beyond the scope of anaesthesiology. The acute hypermetabolic state in MH, resulting in acidosis, heat production and muscular activity is probably due to an inability to control calcium concentration within the skeletal muscle fiber, and may involve a generalized alteration in cellular or subcellular membrane permeability. The susceptibility to develop MH is controlled by several genetic factors. Evaluation of affected families is guided by in vitro analysis of drug-induced contractures in muscle biopsy specimens; a practical and reliable non-invasive test to predict the susceptibility is still being sought. At the present time there is incontrovertible evidence that the hydantoin derivate dantrolene sodium is the only known specific drug in treatment and prophylaxis of MH. A concept for the treatment of MH and guidelines for the management of a patient at risk are presented; medico legal aspects of the complication are stressed.

[An attempt to reconcile differences of opinion in the field of malignant hyperthermia]. / Ein Beitrag zur Beseitigung von Meinungsverschiedenheiten auf dem Gebiet der Malignen Hyperthermie.

Two of the persisting controversies concerning malignant hyperthermia (MH) are discussed: storing and dosage of dantrolene and preoperative tactics to be followed with patients who are MH-susceptible. Reasons are presented for the obligation to store sufficient amounts of dantrolene in every operating suite. The second part discusses the question of pretreatment of MH-susceptible patients with dantrolene.

Effects of short-term infusion of nifedipine or verapamil on systemic hemodynamics and left ventricular myocardial contractility in patients prior to coronary artery bypass surgery.

The effects of short-term infusion (10 min) of nifedipine (7.5 micrograms . kg-1) or verapamil (0.15 mg . kg-1) on left ventricular (LV) contractility and on systemic hemodynamics in patients with coronary artery disease, chronically treated with low-dose beta-adrenergic blocking drugs, exhibiting a normal LV function at rest, are presented. In order to analyze the interaction between calcium entry blocking drugs and halothane, the results are discussed in light of data, obtained in similar patients during halothane anesthesia, using identical experimental conditions, which have already been reported. LV dP/dtmax and LV end-diastolic pressure (LVEDP) remained unaffected when nifedipine was infused in the awake patients. Verapamil significantly decreased LV dP/dtmax in patients while awake, but LVEDP did not change. Both calcium entry blocking drugs caused decreases in blood pressure and systemic vascular resistance, accompanied by increases in heart rate. The only significant differences between the awake and the anesthetized patients were the absence of changes in heart rate and the greater reduction in LV dP/dtmax following administration of the calcium entry blocking drugs during anesthesia. Possible explanations for this may include the drugs' combined interference with calcium ion fluxes within the myocardial and smooth muscle fibers, the ability of halothane to modify the response of the autonomic nervous system to the calcium entry blocking drugs and altered kinetics of the calcium entry blocking drugs induced by the volatile anesthetic. It is impossible to determine from the present investigation which of these mechanisms is predominant.

Nifedipine versus nitroprusside for controlling hypertensive episodes during coronary artery bypass surgery.

Intraoperative hypertensive episodes are a common problem in patients undergoing coronary artery bypass grafting. Twenty patients who developed acute hypertension (mean arterial pressure increase to 110 mmHg) were studied. Ten patients received nifedipine (about 3 micrograms kg-1 min-1) and ten patients nitroprusside (about 0.75 micrograms/kg-1 min-1) to return arterial blood pressure to control levels. All patients were anaesthetized with flunitrazepam, fentanyl, pancuronium and N2O/O2. The study compares the effects of nifedipine and nitroprusside on systemic and pulmonary haemodynamics. Both nifedipine and nitroprusside decreased arterial pressure to baseline values within about 3 min by reducing the elevated systemic vascular resistance. Cardiac filling pressures and pulmonary artery pressure decreased significantly only with nitroprusside. Following nitroprusside cardiac output remained unchanged whereas nifedipine increased cardiac output and stroke volume when blood pressure was lowered by a comparable degree. The data suggest that nifedipine primarily affects resistance vessels in the systemic circulation without significantly changing venous tone as opposed to the effect of nitroprusside. Thus, nifedipine appears to be an appropriate vasodilator for controlling arterial hypertensive episodes in patients with coronary artery disease and normal left ventricular function.

Pulmonary vascular responses to nitrous oxide in patients with normal and high pulmonary vascular resistance.

The pulmonary vascular responses to 50 per cent nitrous oxide were studied in 32 anesthetized patients ventilated to maintain normal PaCO2. One group consisted of sixteen patients with coronary artery disease (CAD) and normal pulmonary vascular resistance (PVR) about to undergo coronary artery bypass surgery. A second group consisted of 16 patients with markedly elevated PVR values due to chronic mitral valve stenosis (MVS). CAD patients showed a significant increase in PVR irrespective of whether halothane or fentanyl was used as background anesthetic. Individual changes, however, did not exceed the upper limit of normal and therefore are not considered to be of clinical importance in these patients. In patients with MVS subjected to fentanyl anesthesia, N2O caused a marked increase in PVR from 357 to 530 dyn . s. cm-5. Halothane anesthesia did not significantly attenuate the effect of nitrous oxide on the pulmonary vasculature as mean PVR increased from 351 to 451 dyn . s. cm-5. These results suggest that the preexisting PVR value is of more importance for the pulmonary vascular response to N2O than the influence of background anesthesia. We conclude that nitrous oxide should be used with caution in patients with elevated pulmonary vascular resistance, particularly in the presence of right ventricular dysfunction and/or right coronary artery disease.

Comparison of isoflurane and halothane when used to control intraoperative hypertension in patients undergoing coronary artery bypass surgery.

The hemodynamic effects of isoflurane and halothane when used to control intraoperative hypertension were evaluated in 20 patients undergoing coronary artery bypass grafting. The patients were anesthetized with flunitrazepam, fentanyl, pancuronium, and N2O-O2. Control measurements were made after skin incision. When mean arterial pressure increased to 110 mm Hg due to sternal spread or surgical manipulation of the aorta, isoflurane or halothane were used to return arterial pressure to control levels. Using a non-rebreathing system, inspired isoflurane concentrations of 1.5-2.0 vol% or halothane concentrations of 1.0-1.5 vol% were necessary. Measurements were repeated during the hypertensive episode and after treatment with isoflurane or halothane while surgical stimulation continued. Both inhalation anesthetics decreased arterial pressure to baseline values within 5-10 min. The lowering of arterial pressure with halothane was not accompanied by significant decreases in the elevated systemic vascular resistance and pulmonary capillary wedge pressure. Cardiac index and stroke volume index decreased markedly when halothane was used (18% and 25%, respectively). In contrast, isoflurane significantly decreased systemic vascular resistance (42%). This reduction of left ventricular afterload was associated with an increase in cardiac index (22%) and a decrease in left ventricular filling pressure. Heart rate did not change significantly. These findings indicate that isoflurane is superior to halothane for controlling intraoperative hypertension during coronary artery bypass surgery.

[Dantrolene in the treatment of life-threatening psychiatric disease pictures. A contribution to the therapy of the malignant neuroleptic syndrome and acute febrile catatonia]. / Dantrolen in der Behandlung lebensbedrohlicher psychiatrischer Krankheitsbilder. Ein Beitrag zur Therapie des malignen neuroleptischen Syndroms und der akuten febrilen Katatonie.

The malignant neuroleptic syndrome and acute febrile catatonia are life-threatening psychiatric disorders which frequently are treated in intensive care units outside psychiatric departments. Their manifestations are very similar to those of anaesthesia-specific malignant hyperthermia. The three syndromes have in common signs of increased muscle metabolism. Dantrolene, a specific drug in the treatment of malignant hyperthermia, has been used successfully several times recently in the treatment of the malignant neuroleptic syndrome. One such case is reported. In a 23-year-old man with signs of acute febrile catatonia parenteral dantrolene and electroconvulsive shocks succeeded in counteracting the symptoms of the abnormally raised muscle metabolism.

Comparison of phentolamine and urapidil in controlling acute intra-operative hypertension in patients subjected to coronary artery bypass surgery.

Intra-operative hypertensive episodes are a frequent problem in patients undergoing coronary artery bypass grafting. The haemodynamic effects of the alpha-adrenergic blocking drugs phentolamine and urapidil, two alpha-adrenergic blocking drugs with a different alpha-receptor subtype specificity, when used to control intra-operative hypertension were evaluated. Ten patients received phentolamine (about 25 micrograms kg-1 min-1) and ten patients received urapidil (about 100 micrograms kg-1 min-1) to return arterial blood pressure to control levels. Both drugs decreased arterial pressure to baseline values within 2-3 minutes by reducing the elevated systemic vascular resistance. Treatment with phentolamine was accompanied by a marked increase in heart rate with a concomitant increase in cardiac index and the rate-pressure product. Urapidil caused no change in heart rate, but the cardiac index increased. Urapidil lowered the rate-pressure product significantly. Both drugs reduced mean pulmonary artery and pulmonary capillary wedge pressures. The different selectivity of phentolamine and urapidil to alpha 1-and alpha 2-adrenergic receptors induces the diverse haemodynamic effects. We conclude that the use of urapidil is the superior regimen when an alpha-adrenergic blocking agent is favoured as a vasodilator.

Postoperative malignant hyperthermia and dantrolene therapy.

A case of malignant hyperthermia (MH) in a three-year eight-month-old girl is presented. Definite symptoms of MH developed in the awake patient 30 min after termination of anaesthesia which had lasted five hours. This postoperative MH-episode resolved promptly following intravenous administration of dantrolene (2.5 mg X kg-1 initially, followed by 5 mg X kg-1 over 12 hours). Results of serial serum samples revealed a steady increase in creatine kinase (CK) concentration with the highest value being observed at the second day, despite dantrolene therapy. The unusual occurrence of MH in the postoperative period, when the major effects of anaesthesia were no longer an important consideration, is discussed with regard to the "human stress syndrome." The necessity to give this information to people usually not familiar in diagnosing MH (e.g., medical personnel in surgical wards) is stressed.

Haemodynamic responses to induction of anaesthesia using midazolam in cardiac surgical patients.

The cardiovascular effects of midazolam 0.2 mg kg-1 i.v. were studied during the induction of anaesthesia in 16 premedicated patients subjected to cardiac surgery. In eight patients with coronary artery disease in whom global resting left ventricular function was normal the haemodynamic changes were small and observations on arterial pressure, cardiac index, stroke index, cardiac filling pressures, systemic and pulmonary vascular resistance appeared to parallel those accompanying deep sleep in healthy volunteers. In eight patients with valvular heart disease and haemodynamic evidence of moderately impaired cardiac performance, pump function during induction with midazolam was maintained, probably as a result of the tendency towards a decrease in systemic vascular resistance. Midazolam appears to be a valuable alternative to conventional induction agents without adverse effects on the cardiovascular system.

[Hemodynamic analysis of 6 different anesthesia induction procedures in coronary surgery patients]. / Hämodynamische Analyse 6 verschiedener Anästhesie-Einleitungsverfahren bei koronarchirurgischen Patienten.

We investigated the cardiovascular effects of intravenous thiopentone (3.0 mg/kg), etomidate (0.3 mg/kg), althesin (0.07 ml/kg), ketamine (1.5 mg/kg), diazepam (0.15 mg/kg) and flunitrazepam (0.015 mg/kg) alone and after the addition of fentanyl (0.01 mg/kg) during induction of anaesthesia in 46 premedicated patients subjected to coronary artery bypass surgery. Thiopentone, etomidate or diazepam caused only small changes in the haemodynamic determinants of myocardial oxygen supply and demand (arterial pressure, heart rate, left and right ventricular filling pressure) in patients with coronary artery disease in whom global resting left ventricular function was normal. Althesin and flunitrazepam produced a significant fall in arterial pressure, cardiac index and stroke index; heart rate increased after the administration of althesin. Ketamine markedly elevated systemic and pulmonary pressure, heart rate, systemic and pulmonary vascular resistance, right and left ventricular filling pressure. The subsequent administration of fentanyl was associated with a further decrease in arterial pressure in the althesin and flunitrazepam group. The circulatory stimulating effects of ketamine were largely abolished by fentanyl. None of the induction procedures was associated with cardiovascular stimulation during laryngoscopy and tracheal intubation.

Isoflurane improves the tolerance to pacing-induced myocardial ischemia.

Fourteen patients with normal, global, left ventricular function scheduled for elective myocardial revascularization were studied at rest and during atrial pacing before and during isoflurane anesthesia (0.5% end-tidal) plus 50% nitrous oxide. Rapid atrial pacing was performed in a stepwise fashion until the onset of angina pectoris in the awake patients. The same step increase in pacing rate was applied in the anesthetized patients. Compared with prepacing baseline values, isoflurane significantly decreased systemic blood pressure, coronary perfusion pressure, the rate-pressure product, and cardiac index. No patient had ST-segment depression while awake or during isoflurane anesthesia before pacing was started. Prepacing left and right ventricular filling pressures and wave forms were normal, both while awake and during isoflurane anesthesia. The mean pacing rate at which first signs of myocardial ischemia appeared (V5 ST-segment depression greater than or equal to 0.1 mV, increase in pulmonary capillary wedge pressure (PCWP) to greater than or equal to 15 mmHg, and prominent PCWP v-waves greater than or equal to 20 mmHg) was significantly higher during isoflurane anesthesia than in the awake patients (128 +/- 4 vs. 115 +/- 5 beats/min). With the exception of one patient, the individual pacing rates inducing first signs of ischemia in the awake patients were below the anginal threshold. None of the patients had a reduced ischemic threshold during anesthesia. Eleven anesthetized patients tolerated a higher pacing rate until initial signs of ischemia appeared. In four of these patients, the pacing rate required to induce first signs of ischemia was above the heart rate at which chest pain had been induced while they were awake. At a peak atrial pacing rate of 129 +/- 5 beats/min, which had induced angina pectoris in the awake patients, the increase in PCWP was significantly smaller during pacing with isoflurane than during control pacing. Prominent PCWP v-waves (greater than or equal to 20 mmHg) appeared in 12 of the 14 patients during initial pacing to angina and in eight patients paced during isoflurane anesthesia. In six of these eight patients, the abnormal v-waves were less prominent than those observed during control pacing. Ischemic ST-segment changes developed in 13 of 14 patients during initial pacing and in nine patients during pacing with isoflurane. Mean V5 ST-segment depression during the two pacing periods was significantly different, averaging 0.19 and 0.11 mV, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)