Comparison of the acute effects on gas exchange of nasal ventilation and doxapram in exacerbations of chronic obstructive pulmonary disease. Effect of doxapram on obstructive sleep apnea. Randomized, controlled, blinded trial of doxapram for extubation of the very low birthweight infant. Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema. Theophylline improves gas exchange during rest, exercise, and sleep in severe chronic obstructive pulmonary disease. Naltrexone improves blood gas patterns in obstructive sleep apnoea syndrome through its influence on sleep. Effects of chlormadinone acetate, acetazolamide and oxygen on awake and asleep gas exchange in patients with chronic obstructive pulmonary disease (COPD). Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. Aminophylline versus doxapram in weaning premature infants from mechanical ventilation: preliminary report.
Nasal intermittent positive pressure ventilation (NIPPV) is useful in exacerbations of chronic obstructive pulmonary disease (COPD) complicated by ventilatory failure. The effects of NIPPV were compared with those of the respiratory stimulant doxapram on gas exchange in patients with COPD and acute ventilatory failure.
                Patients admitted with acute exacerbations of COPD and type 2 respiratory failure (Pao2 < 8 kPa and PaCO2 > 6.7 kPa) who did not improve with conventional treatment were randomised to receive either NIPPV or intravenous doxapram. Blood gas tensions were monitored for four hours.
                In nine patients who received NIPPV the arterial PaO2 improved from a mean (SE) of 5.9 (0.4) kPa to a maximum of 8.1 (0.6) kPa which was maintained at four hours. Eight patients who received doxapram had a similar baseline Pao2 of 5.6 (0.4) kPa which rose to a maximum of 7.3 (0.5) kPa but this was not maintained at four hours. The improvement in Pao2 in patients on NIPPV was accompanied by a fall in Paco2 but, in contrast, in those who received doxapram there was no improvement in Paco2.
                NIPPV may be more effective than doxapram in the management of acute ventilatory failure complicating COPD. To determine whether treatment with a respiratory stimulant, doxapram hydrochloride, would improve obstructive sleep apnea, we administered the drug to four patients with this disease. Subjects were given a bolus of doxapram, 0.5 mg X kg-1 lean body mass, followed by a 1 mg X min-1 infusion throughout the night on one night and placebo another night. Doxapram produced improvement in the average oxyhemoglobin desaturation during apneic and hypopneic episodes and decreased average apnea length, but did not change the average number of oxyhemoglobin desaturations per hour of sleep or sleep efficiency. We conclude that doxapram, when administered at levels known to increase ventilatory drive, does not decrease the number of disordered breathing events during sleep but does cause termination of these events at higher levels of oxyhemoglobin saturation. The objective of the study was to determine whether administering doxapram by infusion to the very low birthweight infant, prior to extubation during the first 3 weeks of life, would increase the incidence of successful extubation. The study patients, 56 infants of less than 1251 g birthweight and less than 30 weeks' gestation, were entered in the first 3 weeks of life when lung disease had started to improve. A randomized blinded trial was performed, with infants receiving 3.5 mg kg(-1) doxapram bolus, followed by an infusion at 1 mg kg(-1) h(-1), or placebo. Weaning from positive pressure ventilation was standardized and extubation occurred after a 12 h trial of an intermittent mandatory ventilation (IMV) rate of 6 breaths min(-1), if PCO2 < 55 mmHg, pH > 7.26, and FiO2 < 0.45. Study drug was continued for 48 h postextubation, and the infants were placed on nasopharyngeal continuous positive airway pressure (CPAP) for 72 h postextubation. Extubation failure within the first 72 h after extubation was objectively defined in terms of acidosis (pH < 7.26), hypercarbia (PCO2 > 55 mmHg), excessive oxygen requirement (FiO2 > 0.8) or frequent apnoea (more than three in 12 h, or more than two requiring face mask IMV in 24 h). No difference was noted in the frequency of successful extubation between the groups. Fifteen infants in each group were successfully extubated before the 10th day of the study. In conclusion, when given in accordance with this protocol doxapram does not increase the likelihood of successful extubation in the very low birthweight infant. Increasing successful extubations in this group of infants will require other strategies. We studied 50 preterm infants who had multiple or traumatic endotracheal intubations, or whose duration of endotracheal intubation was > or = to 14 days, and who were considered at high risk for airway edema. These infants were enrolled in a prospective, randomized, controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress. At study entry, both groups had similar weights, postnatal ages, methylxanthine use, ventilator settings, blood gas values, and pulmonary function test results (dynamic compliance, total respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure, minute ventilation, and peak inspiratory and expiratory flow rates). Patients underwent blood gas studies, physical examinations, and pulmonary function testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to 24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25 mg/kg per dose, at baseline, and then every 8 hours for a total of three doses; 23 infants received saline solution at corresponding times. Eighteen to twenty-four hours after extubation, total pulmonary resistance increased by 225% from baseline in the control group compared with 33% in the dexamethasone group (p < 0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants, 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients (p < 0.006). Of the 23 control patients, 4 required reintubation compared with none of the treated group (p < 0.05). We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight, high-risk preterm infants. The effects of theophylline on pulmonary function and gas exchange during rest, sleep, and exercise were assessed in 10 patients with severe but stable chronic obstructive pulmonary disease (COPD; median FEV1, 31% of predicted). The study was randomized, double blind, placebo controlled, and crossover in design, with each study period lasting 3 wk, and all other usual bronchodilator therapy was continued unchanged. All patients had detailed pulmonary function tests, in addition to exercise testing and overnight sleep studies by standard polysomnography. Theophylline significantly improved gas exchange during rest, exercise, and sleep. Awake resting arterial blood gases showed a higher PaO2 on theophylline (78 [53 to 93] mm Hg, median [range]) than placebo (72 [47 to 83] mm Hg; p < 0.01 by ANOVA), and PaCO2 was lower on theophylline (42 [38 to 54]) compared with placebo (45 [40 to 51], p < 0.05 by ANOVA). Arterial oxygen saturation (SaO2) was significantly higher on theophylline than placebo during exercise and sleep (p < 0.01), and transcutaneous CO2 was lower during sleep (p < 0.05). Theophylline also resulted in significantly improved pulmonary function and reduced trapped gas volume (p < 0.05). Exercise performance was no different during theophylline or placebo phases of the study. Sleep quality, however, was significantly impaired on theophylline. We conclude that theophylline has clinically significant benefits in patients with severe COPD. Endogenous opiates have been shown to depress ventilation, and could therefore play a role in sleep apnoea syndrome (SAS). Hence, opiate antagonists have been used to treat SAS. The improvement they seem to give in blood-gas monitoring could derive either from a direct blocking of endorphins that inhibit respiration or else, indirectly, through an influence on sleep patterns. The present study used a double blind cross-over protocol to investigate the relationships between the effects on blood-gas and on sleep patterns of the oral opiate antagonist naltrexone in obstructive SAS. Sleep patterns and transcutaneous blood gas (tcPO2 and tcPCO2) were recorded in parallel. Control recordings, without treatment, were carried out over two nights, followed by two nights of recording after administration either of naltrexone followed by a placebo or of a placebo followed by naltrexone. The number of obstructive apnoea and hypopnoea events per hour of sleep (Apnoea-Hypopnoea Index: AHI), of hypoxic events (defined as a tcPO2 fall of at least 10, 15 or 20 mm Hg) and of hypercapnic events (defined as a tcPCO2 increase of at least 5 mm Hg) were counted. A Metabolic Suffering Index (MSI) was calculated, defined as the product of the number, duration and magnitude of hypoxic and hypercapnic events. Compared to placebo, naltrexone resulted in significant improvements in blood-gas patterns for the duration and MSI of hypoxic events and for the number, duration and MSI of hypercapnic events. Likewise, compared to placebo, naltrexone induced significant decreases in total sleep time, slow-wave sleep and rapid eye movement (REM) sleep, and, on the other hand, significant increases in total wake time and in the number of wakenings per hour of sleep (Nw h-1). Certain naltrexone-linked blood-gas improvements were closely correlated with certain of the sleep pattern changes: the decrease in number and duration of hypoxic events correlated with REM-time decrease and the decrease in number and duration of hypercapnic events correlated with the increase in Nwh-1. These findings suggest that the improvement in blood-gas patterns induced by naltrexone in SAS may be mediated by sleep pattern effects: i.e. a decrease in REM-time and an increase in intra-sleep wakening. The purpose of this study was to assess the short-term effects of chlormadinone acetate (CMA), a synthetic progestogen, acetazolamide (ACET) and oxygen on awake and asleep blood gas values. The study was conducted according to a randomized, double-blind and placebo-controlled design in 53 hypoxaemic patients with chronic obstructive pulmonary disease. On the first two consecutive nights, all patients received either room air or oxygen, via a nasal cannula, in random order. They then received either CMA (25 mg), ACET (250 mg) or placebo twice a day, all in identical capsules. On the third study night, after one week of drug treatment, the patients were tested breathing room air. CMA and ACET therapy decreased mean daytime arterial carbon dioxide tension (PaCO2) by 0.7 and 0.5 kPa, respectively, and night-time end-tidal carbon dioxide tension (PETCO2) by 0.5 and 0.3 kPa, respectively. Supplemental oxygen caused increased CO2 retention during the day and night (0.6 and 0.3 kPa, respectively. Daytime arterial oxygen tension (PaO2) increased to the same extent during ACET (1.9 kPa) and oxygen (2.5 kPa). Asleep oxygen saturation improved most with oxygen supplementation (7%), although ACET also caused significant improvement (4%). CMA administration had virtually no effect on mean awake and asleep hypoxaemia. ACET therapy significantly improved subjective sleep quality. On CMA, minute ventilation increased in association with an augmentation of the hypercapnic ventilatory response. ACET treatment increased both hypercapnic and hypoxic ventilatory responses. We conclude from the group of patients with COPD studied, that the short-term effects of ACET treatment on gas exchange compare favourably with those of CMA. Oxygen therapy improves oxygenation slightly more than ACET, but aggravates CO2 retention. To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome.
                Randomised controlled trial with double blinding between inotrope groups. Setting: York District Hospital, England.
                138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. Interventions: Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care.
                Hospital mortality and morbidity.
                Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P=0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital.
                Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care. A small, double-blind crossover study compared the efficacy of aminophylline and doxapram in ventilator weaning of eight premature infants recovering from respiratory distress syndrome (RDS). Although neither drug was significantly better than the other, four infants were weaned from mechanical ventilation after drug administration. It is suggested that drugs stimulating the respiratory center may aid in shortening the duration of mechanical ventilation in premature infants recovering from RDS.
Doxapram can improve blood gas exchange over the first few hours of treatment. Newer techniques such as non-invasive ventilation may prove to be more effective, although there is no randomised trial evidence to this effect.