Sten G. E. Lindahl

Dramatic effect on oxygenation in patients with severe acute lung insufficiency treated in the prone position.

OBJECTIVE To confirm the positive effect of prone positioning on oxygenation in patients with acute lung insufficiency. DESIGN Clinical follow-up study. SETTING The intensive care unit at a tertiary care academic hospital. PATIENTS Thirteen patients suffering from severe acute lung insufficiency caused by trauma, septicemia, aspiration, and burn injury. Eleven of the patients had severe hypoxia (oxygenation indices [PaO2/FIO2] < or = 80 torr [< or = 10.7 kPa]). Patients > 70 yrs of age were excluded from the study. INTERVENTIONS Treatment in the prone position without changing other ventilatory settings than FIO2 when saturation increased. MEASUREMENTS AND MAIN RESULTS Twelve of the 13 patients responded to treatment in the prone position. The patient that did not respond improved her gas exchange when nitric oxide was instituted. She died, however, from a Gram-negative septicemia. No patient needed extracorporeal membrane oxygenation. Apart from the settings of FIO2 when saturation increased, the ventilatory settings were unchanged. In the prone position, the oxygenation index increased (p < .0002) and the alveolar-arterial oxygen gradient, P(A-a)O2, decreased dramatically (p < .0001). CONCLUSIONS The prone position significantly improves impaired gas exchange due to severe acute lung insufficiency. It is suggested that this treatment is used before more complex modalities.

Opioid Action on Respiratory Neuron Activity of the Isolated Respiratory Network in Newborn Rats

BackgroundUnderlying mechanisms behind opioid-induced respiratory depression are not fully understood. The authors investigated changes in burst rate, intraburst firing frequency, membrane properties, as well as presynaptic and postsynaptic events of respiratory neurons in the isolated brainstem after administration of opioid receptor agonists. MethodsNewborn rat brainstem–spinal cord preparations were used and superfused with &mgr;-, &kgr;-, and &dgr;-opioid receptor agonists. Whole cell recordings were performed from three major classes of respiratory neurons (inspiratory, preinspiratory, and expiratory). ResultsMu- and &kgr;-opioid receptor agonists reduced the spontaneous burst activity of inspiratory neurons and the C4 nerve activity. Forty-two percent of the inspiratory neurons were hyperpolarized and decreased in membrane resistance during opioid-induced respiratory depression. Furthermore, under synaptic block by tetrodotoxin perfusion, similar changes of inspiratory neuronal membrane properties occurred after application of &mgr;- and &kgr;-opioid receptor agonists. In contrast, resting membrane potential and membrane resistance of preinspiratory and majority of expiratory neurons were unchanged by opioid receptor agonists, even during tetrodotoxin perfusion. Simultaneous recordings of inspiratory and preinspiratory neuronal activities confirmed the selective inhibition of inspiratory neurons caused by &mgr;- and &kgr;-opioid receptor agonists. Application of opioids reduced the slope of rising of excitatory postsynaptic potentials evoked by contralateral medulla stimulation, resulting in a prolongation of the latency of successive first action potential responses. ConclusionsMu- and &kgr;-opioid receptor agonists caused reduction of final motor outputs by mainly inhibiting medullary inspiratory neuron network. This inhibition of inspiratory neurons seems to be a result of both a presynaptic and postsynaptic inhibition. The central respiratory rhythm as reflected by the preinspiratory neuron burst rate was essentially unaltered by the agonists.

Posture primarily affects lung tissue distribution with minor effect on blood flow and ventilation

We used quantitative single photon emission computed tomography to estimate the proportion of the observed redistribution of blood flow and ventilation that is due to lung tissue shift with a change in posture. Seven healthy volunteers were studied awake, breathing spontaneously. Regional blood flow and ventilation were marked using radiotracers that remain fixed in the lung after administration. The radiotracers were administered in prone or supine at separate occasions, at both occasions followed by imaging in both postures. Images showed greater blood flow and ventilation to regions dependent at the time of imaging, regardless of posture at radiotracer administration. The results suggest that a shift in lung parenchyma has a major influence on the imaged distributions. We conclude that a change from the supine to the prone posture primarily causes a change in the vertical distribution of lung tissue. The effect on the vertical distribution of blood flow and ventilation within the lung parenchyma is much less.

Cyclooxygenase inhibition for postoperative analgesia

T he anesthesiologist has a central role in the management of acute postoperative pain, and effective management has been clearly demonstrated to improve clinical outcomes (1,2). Acute pain can rapidly evolve into chronic pain, and the two should not be viewed as separate entities (3). Failure to achieve effective analgesia is a major predictive factor for the conversion of acute postoperative pain to chronic pain after several different types of surgery (4). Traditionally, opioids and local anesthetics have been the pharmacological foundation for postoperative pain management; however, optimization has been difficult because of anxieties regarding deleterious side effects. Opioids may cause respiratory depression, oversedation, and prolongation of postoperative ileus. Regional anesthetic techniques are limited by the requirement for special monitoring and the irreversibility of neuronal blockade once it is instituted. The effectiveness of nonsteroidal antiinflammatory drugs (NSAIDs) in alleviating pain and reducing requirements for opioids in the postoperative period has been well documented (5–7), but concerns regarding gastropathy, renal dysfunction, and hemostatic defects have limited their use. There is further anxiety because fasting and the frequent prevalence of hypovolemia in the postoperative period may potentiate gastric and renal side effects. Do anesthesiologists underuse NSAIDs as perioperative analgesics because of exaggerated anxieties regarding side effects and inadequate information regarding mode of action? This review article describes prostaglandin (PG) biosynthesis and the central role of cyclooxygenase (COX) expression in pain perception, and then it focuses on the potential side effects of COX inhibition. Goals of Postoperative Analgesia The goal of postoperative pain relief is to achieve optimal analgesia, facilitating a speedy return to normal physiological organ function with minimal side effects. Anesthesiologists must also try to reduce the incidence of chronic pain after surgery by effective treatment of acute postoperative pain. Minimization of opioid and local anesthetic side effects is a major consideration, and here NSAIDs have great potential. This process begins at the preoperative assessment, when the anesthesiologist must identify patients at increased risk of NSAID-induced complications. Although renal failure, allergy, and late pregnancy are absolute contraindications, a history of peptic ulcer disease, congestive cardiac failure, or cirrhosis, previous thrombosis, and concomitant corticosteroid therapy require further consideration before being classed as contraindications. A history of NSAID consumption for other conditions, such as arthritis, is reassuring, and a normal creatinine clearance will allay fears regarding postoperative renal failure.

Actions of enflurane, isoflurane, vecuronium, atracurium, and pancuronium on pulmonary resistance in dogs.

The effects of enflurane, isoflurane, vecuronium, atracurium, and pancuronium on pulmonary resistance and heart rate were studied in 30 vagotomized dogs lying supine and anesthetized with chloralose-urethane. None of the five drugs affected pulmonary resistance when the airway was unstimulated. Enflurane and isoflurane significantly attenuated the increase in pulmonary resistance induced by electrical stimulation of the vagus nerves. This effect was dosedependent and similar for both anesthetics at equivalent multiples of their minimum alveolar concentration. Atracurium significantly (P < 0.05) enhanced the increase in pulmonary resistance induced by vagus nerve stimulation; vecuronium had no significant effect. Pancuronium, up to a cumulative dose of 0.14 mg/kg, also significantly (P < 0.05) enhanced the increase in pulmonary resistance induced by vagus nerve stimulation; but this effect was reversed by further increasing the dose. Pancuronium also attenuated the cardiodecelerator response to vagus nerve stimulation in a dose-depen-dent fashion. The underlying mechanisms for the attenuation of responses to vagus nerve stimulation by enflurane or isoflurane or for the increase in response with atracurium are unknown. Pancuronium at lower doses increases the response most likely by blocking prejunctional muscarinic receptors (M2) that physiologically inhibit vagally mediated increases in pulmonary resistance.

Thermogenesis in Brown Adipocytes Is Inhibited by Volatile Anesthetic Agents A Factor Contributing to Hypothermia in Infants

BackgroundIn Infants, nonshivering thermogenesis from brown adipose tissue provides an important source of heat for thermoregulation. Infants are known to have a high susceptibility to hypothermia during anesthesia. To investigate whether this could be due to an inhibition of nonshivering thermogenesis by anesthetics, the effect of preincubation with volatile anesthetics on the norepinephrine-induced heat production of brown adipocytes was investigated. MethodsBrown adipocytes from hamsters were isolated with a collagenase digestion method and preincubated with volatile anesthetics. The cells were stimulated with norepinephrine, and heat production, measured as oxygen consumption, was monitored polarographically. ResultsNorepinephrine addition led to a 20-fold increase in the rate of oxygen consumption (thermogenesis). However, preincubation of cells with 3% halothane reduced the response to norepinephrine by more than 70%. The potency of norepinephrine (the median effective concentration) was not affected by halothane. Full effect of halothane was reached quickly, and after halothane withdrawal, the thermogenic response recovered, although rather slowly. Halothane, isoflurane, and enflurane were approximately equipotent inhibitors of thermogenesis, with concentrations of approximately 0.7% resulting in 50% inhibition. The inhibitory effect of 1% halothane was unaffected by the presence of 74% nitrous oxide, but nitrous oxide alone also reduced thermogenesis. ConclusionsVolatile anesthetics severely attenuated the thermogenic response to norepinephrine of isolated brown-fat cells. It is inferred that brown-adipose-tissue heat production is reduced during (and probably also some time after) anesthesia. Because infants are dependent on brown-fat-de-rived nonshivering hermogenesis for thermal balance, the inhibition by volatile anesthetic agents of brown-adipocyte heat production may at least partly explain the susceptibility of infants to hypothermia during and after anesthesia.

Actions of opioids on respiratory activity via activation of brainstem μ-, δ- and κ-receptors; an in vitro study

Abstract Opioid-induced respiratory depression is well documented. However, exact sites of action and mechanisms for opioid-induced effects on respiration have not yet been elucidated. The present study was carried out on isolated brainstem–spinal cord preparations from newborn rats in order to explore the opioid activity on brainstem μ-, δ- and κ-receptors. The brainstem–spinal cord was isolated from 0- to 4-day-old Sprague-Dawley rats. The preparation was perfused with artificial cerebrospinal fluid (28.5°C) equilibrated with 95% O2 and 5% CO2 at a pH of 7.4. Neuronal respiratory activity was recorded from the ventrolateral part of the medulla oblongata and efferent impulses from C4 or C5 ventral roots. Effects of the μ-receptor agonist DAGO, the δ-receptor agonist DPDPE and the κ-receptor agonist U50,488 on respiratory frequency (fR), inspiratory time (Ti) and peak integrated C4 amplitude (IntC4) were measured. In addition, the effect of pre-treatment with the μ1 receptor antagonist naloxanazine (35 mg/kg, subcutaneous injection) was evaluated. DAGO reduced fR and Ti in a concentration-dependent manner and caused a reduction of IntC4 at high concentrations (10 μM). The μ1 receptor antagonist naloxanazine shifted the fR concentration–response curve for DAGO to the right (P

Amino acid-induced thermogenesis reduces hypothermia during anesthesia and shortens hospital stay.

UNLABELLED Amino acid infusion during general anesthesia induces thermogenesis and prevents postoperative hypothermia and shivering. We propose that amino acid prevention of hypothermia during anesthesia shortens the hospital stay. Core temperatures and pulmonary oxygen uptake were measured in 45 patients, receiving an IV amino acid mixture, 126 mL/h, before and/or during isoflurane anesthesia and 30 control patients receiving acetated Ringers solution. At awakening, mean core temperature was 36.5 degrees+/-0.1 degrees C in the amino acid group and 35.7 degrees+/-0.1 degrees C (P < 0.001) in the controls. Energy expenditure increased by 54%+/-9% from baseline in amino acid patients in whom shivering was uncommon, but only by 5%+/-4% (P < 0.001) in control patients, of whom the majority developed postoperative shivering. The estimated difference in hospital stay between the two groups was 2.7 days (CI 95%: 1.3-4.0). Multiple regression analysis showed that the variables best predicting hospitalization were duration of surgery, amino acid treatment, and awakening temperatures. Duration of surgery was similar in the two groups and core temperatures at awakening were a result of amino acid infusion, which indicates that amino acid infusion during anesthesia and surgery was the most important factor for the shorter hospitalization. IMPLICATIONS Amino acid infusion during general anesthesia induces thermogenesis and prevents postoperative hypothermia and shivering. Multiple regression analysis indicated that this resulted in a shorter hospital stay.

Halothane Selectively Inhibits Nonshivering Thermogenesis Possible Implications for Thermoregulation during Anesthesia of Infants

Background During halothane anesthesia, infants fail to increase oxygen consumption in response to a cold stimulus in the form of an increase in temperature gradient between body and environment. Based on recent observations with isolated brown‐fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshivering thermogenesis during halothane anesthesia. Methods The rate of oxygen consumption was measured in cold‐acclimated hamsters and rats. The rate evoked by norepinephrine injection in hamsters at an environmental temperature of [nearly equal] 24 degrees Celsius was used as a measure of the capacity for nonshivering thermogenesis. Anesthesia was induced by 3% halothane and maintained by 1.5% halothane. One experimental series with spontaneously breathing hamsters and a second control series with spontaneously breathing rats and with rats whose lungs were mechanically ventilated were conducted. Results Norepinephrine injection led to a fourfold increase in the rate of oxygen consumption in control hamsters; after this response had subsided, a second injection led to a similar effect. Halothane anesthesia caused an approximately 20% decrease in resting metabolic rate (P < 0.05) and a 70% inhibition of the thermogenic response to norepinephrine (P < 0.001). The halothane concentration yielding half‐maximal inhibitory effect was estimated to be less than 1.0%. After the animals had recovered from halothane anesthesia, a completely restored thermogenic response to norepinephrine was observed. The inhibitory effect of halothane also was observed in hamsters maintained at normothermia and was therefore not secondary to the slight hypothermia that otherwise developed during anesthesia. In a series of control experiments, it was confirmed that rats also showed large thermogenic responses to norepinephrine injections, and it was found that, in spontaneously breathing halothane‐anesthetized rats, the thermogenic response to norepinephrine was also much inhibited. Further, in halothane‐anesthetized rats whose lungs were mechanically ventilated, and where blood gases were kept at virtually normal levels, the thermogenic response to norepinephrine was found to be similarly markedly inhibited. Conclusions A much diminished or abolished thermogenic response to injected norepinephrine was demonstrated in halothane‐anesthetized animals. This implies that there would be a diminished ability to elicit nonshivering thermogenesis even when this process is physiologically induced. Such a diminished ability could in part explain the susceptibility of neonates and infants to hypothermia during halothane anesthesia.

Relationship Between Invasive and Noninvasive Measurements of Gas Exchange in Anesthetized Infants and Children

Minute ventilation (VE), tidal volume (VT), carbon dioxide elimination (VCO2), and end-tidal (PETCO2) and arterial CO2 tensions (PaCO2) were measured in 39 anesthetized infants and children with body weights ranging from 3.1 to 31 kg. Eighteen children had normal cardiopulmonary function, seven had acyanotic congenital heart disease, and 11 had cyanotic congenital heart disease. One child had left heart failure and pulmonary congestion, and two had severe parenchymal lung disease. To evaluate differences between pulmonary gas exchange calculated from PaCO2 versus PETCO2, dead space volume (VD) and alveolar ventilation (VA) based on a PaCO2 (VDa, VAa) as well as on PETCO2 (VDET, VAET) were performed, and correlations between PaCO2 – PETCO2, VDa/VT – VDET/VT, and VAa – VAET were carried out. It was demonstrated that in normal children, as well as in those with acyanotic congenital heart disease, PETCO2 correlated closely with PaCO2 (r = 0.94, 0.98, respectively). In children with cyanotic congenital heart disease, however, correlation between PETCO2 and PaCO2 was relatively poor (r = 0.61). Mean values for PaCO2 were significantly higher than PETCO2 in the cyanotic children (P < 0.01), resulting in significant underestimation of physiologic dead space (P < 0.05) and significant overestimation of alveolar ventilation (P < 0.01). In three patients with pulmonary disease, large differences between PaCO2 and PETCO2 were comparable with those observed in the children with cyanotic congenital heart disease. It is concluded that in normal children and in children with acyanotic heart disease during anesthesia, noninvasive measurement of PETCO2 can be used as a reliable estimate of PaCO2 and for calculations of physiologic dead space and alveolar ventilation. In children with cyanotic congenital heart disease and severe pulmonary disease, PETCO2 does not provide a precise estimate of PaCO2, and calculations of physiologic dead space and alveolar ventilation should be based on direct measurements of PaCO2.