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Apneic spells associated with timolol therapy in a neonate.

A 2-week-old premature child with congenital glaucoma secondary to anterior cleavage syndrome was treated with timolol maleate and cyclocryotherapy. The patient had apneic spells of up to 30 seconds that stopped soon after timolol maleate therapy was discontinued. No apnea was seen before timolol maleate administration, and no further spells were noted after subsequent cyclocryotherapy without timolol maleate treatment. Possible central nervous system toxicity of timol maleate or its metabolic by-products in neonates with immature blood-brain barriers was noted.

Acetazolamide↗

Abnormal breathing patterns.

In health, breathing is regular and the respiratory rate is sufficiency constant to be useful as a vital sign of health and disease. This regularity depends on a complex interplay of chemical and neural control systems that operate automatically to reset the rate and depth of breathing as changes occur in posture and activity, to adjust the level of ventilation so that changes in gas tensions and pH in the blood and in the brain intersitial fluid are exceedingly modest despite wide swings in metabolic rate and in environmental conditions, and to coordinate ventilation and circulation so that the requirements of individual tissues for O2 delivery and CO2 removal are satisfied. Two broad categories of disorders can result from malfunction of these systems (Table 1): (1) disproportionate ventilation (too high or too low) for the level of metabolic activity, thereby producing severe abnormalities in blood gas tensions or in acid-base balance, and (2) an irregular breathing pattern without eliciting gross changes in blood gas tensions or in acid-base balance. Because of the complexity of the control system, each of these categories represents a final common pathway that can be produced in different ways. In this presentation, we will attempt to describe the general features that characterize the operation of the control system and some new technics that make it possible to trouble-shoot the malfunctioning system in order to identify the mechanism(s) responsible for the abnormality in breathing pattern.

Animals↗

Effects of thiopentone sodium, methoxyflurane and halothane on haematological parameters in sheep during prolonged anaesthesia.

1. Satisfactory surgical anaesthesia in sheep was achieved by i.v. injection of thiopentone sodium per se (20 mg/kg); and also with thiopentone/methoxyflurane and thiopentone/halothane anaesthetics (2--3% and 1.5--2%, respectively). 2. Cardiac arrhythmias were not observed during thiopentone sodium, thiopentone/methoxyflurane and thiopentone/halothane anaesthesia. However, during thiopentone anaesthesia, one sheep displayed a high degree of sinus tachycardia followed with ventricular tachycardia. 3. Pneumograms recorded during thiopentone sodium and thiopentone/methoxyflurane anaesthesia showed no irregularity, but in thiopentone/halothane anaesthesia, 30% of the sheep developed Cheyne-Stokes periodic respiration. 4. Packed cell volume (PCV) and haemoglobin (Hb) were significantly decreased in thiopentone/methoxyflurane and thiopentone anaesthetized sheep, but not in animals anaesthetized by thiopentone/halothane. 5. White blood cell count (WBC) was significantly decreased only in thiopentone/methoxyflurane anaesthetized sheep, but was not remarkable in thiopentone and thiopentone/halothane anaesthetized animals. 6. A significant lymphocytopenia occurred in thiopentone/methoxyflurane and in thiopentone/halothane anaesthetized sheep, but not in the thiopentone anaesthetized animals. This was accompanied with an increase in neutrophils. 7. Clotting time fell, but the extent and time course was different in thiopentone, thiopentone/methoxyflurane and thiopentone/halothane anaesthesia. 8. From these data, it is suggested that thiopentone sodium, thiopentone/methoxyflurane and thiopentone/halothane have different effects on different blood parameters during prolonged anaesthesia, and may be clinically significant.

Anesthesia↗

Aminophylline increases cerebral metabolic rate and decreases anoxic survival in young mice.

In weanling mice treated with pharmacologic doses of aminophylline, the concentrations of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in the brain increased 44 and 36 percent, respectively, and the cerebral metabolic rate was three times that in controls. In neonatal mice, therapeutic doses of aminophylline greatly decreased the rate of anoxic survival in vivo and the duration of gasping of the isolated head. The findings suggest caution in the use of this drug and other methylxanthines in hypoxic human newborns.

Adenine Nucleotides↗

Oscillation and chaos in physiological control systems.

First-order nonlinear differential-delay equations describing physiological control systems are studied. The equations display a broad diversity of dynamical behavior including limit cycle oscillations, with a variety of wave forms, and apparently aperiodic or "chaotic" solutions. These results are discussed in relation to dynamical respiratory and hematopoietic diseases.

Cheyne-Stokes Respiration↗

Analysis of lung ventilation in the aestivating lungfish Protopterus aethiopicus.

During aestivation, the breathing pattern of the lungfish changed from the usual aquatic pattern of a single breath followed by prolonged apnea to the pattern of alternating tachypnea and apnea that characterizes Cheyne-Stokes breathing. As aestivation continued, the number of breaths per tachypneic period increased gradually to reach a steady level at about the 3rd mo. During the bouts of tachypnea, minute ventilation increased because of the increase in respiratory frequency even though tidal volumes decreased. Ventilation of the lungs during aestivation appeared to involve the same mechanism as during life in water, i.e., a buccal force pump. The breathing cycle began with the aspiration of air into the mouth as the buccal cavity enlarged. Lung deflation then occurred abetted by contraction of the abdominal muscles. Lung inflation followed and involved the "swallowing" of air form the posterior buccal region into the lungs. Cycles of deflation and partial inflation of the lungs were repeated 8-40 times (tachypneic period). At the end of the tachypneic cycle, after the last deflation, a series of larger buccal force-pump maneuvers reinflated the lungs before the start of the apneic period.

Adaptation, Physiological↗

Changes in local cerebral blood flow following profound systemic hypotension.

The authors studied local cerebral blood flow in monkeys rendered hypotensive by infusion of a ganglionic blocking agent. Application of the 14C-antipyrine method demonstrated that the blood flow: 1) normally varies reproducibly from one structure to another within the brain; 2) appears at its lowest level in all structures during the early minutes of a rapid-onset hypotension; 3) maintains the same general rank order of blood flow rate during hypotension as was present during normotension; and 4) returns to supranormal levels immediately following the rapid restoration of blood pressure. The values for local cerebral blood flow remain close-to-normal in some animals and diminish significantly in others during late recovery from hypotension. The close-to-normal values accompany uncomplicated recoveries while the diminished values appear in those animals which became neurologically depressed. Areas of the brain considered predisposed to hypotensive injury did not exhibit depressions in blood flow rate during hypotension more markedly than did other brain areas. The present results are interpreted as strong evidence against the "border zone" hypothesis.

Animals↗

[Combined effects of hypoxia and hypercapnia on the functional state of the respiratory center].

Experiments were conducted on cats under nembutal anesthesia; a study was made of pulse activity of bulbar respiratory neurons, electrical activity of the diaphragm and of the intercostal muscles; pO2, pCO2, pH, arterial blood oxygen saturation were determined in combined action of hypoxia and hypercapnia. When hypoxic gaseous mixture was given for respiration the developing hypocapnia disturbed the discharge rhythmic activity of the respiratory neurons, the respiration acquiring a pathological character of the Cheyne--Stokes type. After addition to the hypoxic gaseous mixture of 2% CO2 the gaseous composition of the arterial blood approached the initial values; this addition prevented the development of hypercapnia and disturbances of rhythmic discharge activity of the respiratory neurons. Addition of 5% CO2 to the hypoxic gaseous mixture produced a negative effect: at first it intensified and then depressed the pulse activity of the respiratory neurons, caused metabolic and respiratory acidosis, and promoted asphyxia.

Animals↗

Monitoring as anesthesia draws to a close.

The closing phase of anesthesia is defined. Some of the hazards of this period are reported and illustrated by capnograms. It is claimed that the dangers arising at the end of anesthesia are insufficiently appreciated.

Anesthesia↗

Hypersomnia and periodic breathing. Report of a case and review of the literature.

A patient with hypersomnia and periodic breathing has been studied. Both airflow obstruction and an abnormally of the respiratory control mechanism were implicated in the pathogenesis of the ventilatory arrhythmia. It is suggested that the older terms "Pickwick" syndrome and primary alveolar hypoventilation are abandoned for more descriptive terms, e.g. "hypersomnia with periodic breathing".

Adult↗

The definition of "Cheyne-Stokes rhythms".

The review of the literature on Cheyne-Stokes respiratory periods reveals enormous variation of the opinions expressed. The original description concerned periodicity characterized by rhythmic changes of respiratory phases and respiratory pauses in a relation of 60 : 15 seconds. In the respiratory phase there were 30 respirations of increasing depths and frequency at the beginning of the phase and decreasing depths and frequency at the end of the phase. Literature data about Cheyne-Stokes respiration comprise a multiplicity of all rhythymic forms. The duration of respiratory cycles varies between 12 and 130 seconds. The relation of the respiratory phase and respiratory pause between 6 : 4 or 75 : 70 seconds, and the number of breaths between 3 and 30 during one respiratory phase. Cheyne-Stokes periods were observed in health subjects as well as in patients with neurological, neurosurgical, cardiac, pulmonary and paediatric diseases. Cheyne-Stokes periods were explained as sequel of prolongation of circulation time between pulmonary alveoli and respiratory centre, through increased sensitivity of the respiratory centre to CO2, diminished sensitivity of the respiratory centre to CO2 and O2-deficit, local blood flow disturbances, section of pathways in the brain stem with disinhibition of basic rhythms, brain immaturity, alterations of consciousness, and respiratory obstructions. Rhythmic changes of the heart beat, of excitability of the heart muscle, of blood pressure, of EEG and of neurological and mental signs were observed. In spite of numerous observations detailed analysis of the respiratory cycle was performed in only a few cases. Major studies are lacking.

Animals↗

Variability of the respiratory phase, respiratory pause, and numbers and durations of respirations during periodic breathing.

The analysis of cycles of periodic breathing (Cheyne-Stokes rhythms) in 35 patients showed wide variability of mean values of respiratory phases. The respiratory pauses are usually shorter and the scatter of the mean values is smaller. Only in four cases were respiratory pauses longer than respiratory phases. The duration of the respiratory phase becomes extended through the increase of number of single respirations. The latter also shows a very small scatter. The respiratory rate in 32 out of 35 patients was higher than normal and is to be considered as tachypnoea.

Brain Diseases↗

Experimentally induced Cheyne-Stokes breathing.

We have studied the propensity for periodic breathing to occur in cats anaesthetized with pentobarbitone breathing either spontaneously or with the aid of a 'servo-respirator' governed continuously by the efferent phrenic nerve activity. Sustained periodic breathing could be induced increasing 'controller gain', either by increasing the gain of the respirator, or by lung deflation, which reflexly increased controller responses to both hypoxia and hypercapnia. Periodic breathing was potentiated both by hypoxia and by diminishing the central (CO2, H+)-drive by focal cooling at the ventral surface of the medulla, two procedures which increase the relative influence of hypoxic drive. Less hypoxia was needed to produce periodic breathing at high rather than low controller gains. Reducing controller gain to zero by constant artificial respiration always abolished periodic breathing. Periodic breathing was also eradicated when the relative importance of CO2 drive was enhanced by breathing the cats with CO2-enriched gas mixtures or with 100% O2. The results are consistent with theoretical predictions for the occurrence of oscillations in the mechanisms for the chemical control of breathing and indicate that increasing controller gas can produce periodic breathing. The results further emphasize the importance of the (CO2, H+)-drive in preserving ventilatory stability.

Animals↗