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PubMed1975

[Effects of 1-ethyl-4-(2-morpholinoethyl)-3, 3-diphenyl-2-pyrrolidinone hydrochloride hydrate (doxapram) on the transmural stimulation and reactiontonicotine of the isolated guinea pig heart atrium].

It has been reported that doxapram exhibits a remarkable stimulating effect on respiration in humans and various experimental animals. The present experiment was an attempt to investigate whether or not doxapram inhibits an atrial arrest induced by transmural stimulation and exogenously applied nicotine. Doxapram and dimorpholamine used as comparative agents showed transient and slightly positive responses followed by a negative one in the atrium preparation. Transmural stimulation under a condition of 30 V intensity with 0.3 msec duration at a frequency of 10 Hz for 2 sec caused an atrial arrest for about 3 sec followed by negative chronotropic and inotropic responses, and a positive one. All responses caused by transmural stimulation were hardly affected by pretreatment with doxapram at a concentration of 10(-5) g/ml or less, while dimorpholamine at a high concentration (10(-5)g/ml) showed an inhibition of atrial arrest and following negative responses. Negative chronotropic and inotropic responses caused by an application of nicotine were significantly inhibited by pretreatment with doxapram or dimorpholamine. Both doxapram and dimorpholamine at higher concentrations also inhibited the positive responses of the atrium caused by nicotine. Neither doxapram nor dimorpholamine affected the ACh-induced responses. NA-induced responses were uneffected by pretreatment with doxapram, while the responses were slightly potentiated by dimorpholamine. The action mechanisms of doxapram and dimorpholamine are discussed.

Acetylcholine↗
PubMed2004

Doxapram treatment for apnea in preterm infants.

BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Doxapram has been used to stimulate breathing and so prevent apnea and its consequences. OBJECTIVES: In preterm infants with recurrent apnea, does treatment with Doxapram lead to a clinically important reduction in apnea and use of intermittent positive airways pressure (IPPV), without clinically important side effects? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), MEDLINE from 1966 - June 2004, EMBASE from 1980 - June 2001, CINAHL from 1982- June 2004. Text words 'doxapram', 'apnea or apnoea' and the MeSH term 'infant, premature' were used. Previous reviews including cross references, abstracts from conferences and symposia proceedings were also examined. Abstracts of the Society for Pediatric Research were searched from 1996 - 2004 inclusive. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which doxapram was used for the treatment of apnea in preterm infants were included. DATA COLLECTION AND ANALYSIS: Each author evaluated the papers for quality and inclusion criteria. Independent data extraction was carried out. MAIN RESULTS: Only one trial, which randomized 11 infants to intravenous doxapram and 10 infants to placebo, was found. There were fewer treatment failures after 48 hours in the group of preterm infants treated with doxapram (4/11) compared with the group treated with placebo (8/10). The wide confidence intervals made this result non-significant [RR 0.45 (0.20, 1.05)]. Only one infant, who was from the placebo group, was given IPPV. Of the seven responders by 48 hours in the group of 11 who received doxapram, five failed to respond between 48 hours and seven days after commencement of therapy. This gives a late failure rate of 9/11, similar to the short term failure rate in the placebo group of 8/10. It is not possible to evaluate the late responses of all those in the placebo group since they crossed over to a treatment arm. REVIEWERS' CONCLUSIONS: Although intravenous Doxapram might reduce apnea within the first 48 hours of treatment, there are insufficient data to evaluate the precision of this result or to assess potential adverse effects. No long term outcomes have been measured. Further studies are needed to determine the role of this treatment in clinical practice.

Aminophylline↗
PubMed1991

Effects of doxapram on ionic currents recorded in isolated type I cells of the neonatal rat carotid body.

Whole-cell patch-clamp recordings were used to investigate the effects of the respiratory stimulant doxapram on K+ and Ca2+ currents in isolated type I cells of the neonatal rat carotid body. Doxapram (1-100 microM) caused rapid, reversible and dose-dependent inhibitions of K+ currents recorded in type I cells (IC50 approximately 13 microM). Inhibition was voltage-dependent, in that the effects of doxapram were maximal at test potentials where a shoulder in the current-voltage relationship was maximal. These K+ currents were composed of both Ca(2+)-activated and Ca(2+)-independent components. Using high [Mg2+], low [Ca2+] solutions to inhibit Ca(2+)-activated K+ currents, doxapram was also seen to directly inhibit Ca(2+)-independent K+ currents. This effect was voltage-independent and was less potent (IC50 approximately 20 microM) than under control conditions, suggesting that doxapram was a more potent inhibitor of the Ca(2+)-activated K+ currents recorded under control conditions. Doxapram (10 microM) was without effect on L-type Ca2+ channel currents recorded under conditions where K+ channel activity was minimized and was also without significant effect on K+ currents recorded in the neuronal cell line NG-108 15, suggesting a selective effect on carotid body type I cells. The effects of doxapram on type I cells show similarities to those of the physiological stimuli of the carotid body, suggesting that doxapram may share a similar mechanism of action in stimulating the intact organ.

Animals↗
PubMed1989

Doxapram and the neuromuscular junction.

We have studied the action of doxapram on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. Doxapram augmented neuromuscular transmission in a dose-related manner when a threshold concentration of 5 x 10(-5) mol litre-1 had been exceeded. The activity of the acetylcholinesterase in rat diaphragm has been examined also in the presence of doxapram. No inhibitory effect was seen in the concentration range which augmented neuromuscular transmission, thus excluding cholinesterase inhibition as the underlying mechanism. In contrast, in the presence of partial neuromuscular block, a dose-related depression of neuromuscular transmission with doxapram was revealed. This was greatest when the neuromuscular blocking agents possessed significant presynaptic activity (beta-bungarotoxin and tubocurarine). In this situation any facilitatory action of doxapram was severely reduced or abolished. In contrast, the facilitatory effects of doxapram were apparent in the presence of partial block produced by agents with less or no presynaptic activity (pancuronium and alpha-bungarotoxin). This study suggests that doxapram has a presynaptic facilitatory action at the neuromuscular junction. In the presence of partial neuromuscular block, an inhibitory action is revealed which may be post-junctional. The concentrations of doxapram at which these effects appear are approximately five times greater than those reached in plasma after a standard clinical dose.

Acetylcholinesterase↗
PubMed1991

Interaction of doxapram and pentobarbital in mice.

We found a statistically significant increase in duration of pentobarbital-induced narcosis in doxapram-treated mice. The influence of doxapram (a respiratory stimulant) pretreatment on pentobarbital metabolism in mice was assessed by measurements of sleeping times, hypothermia, LD50 values, hepatic microsomal metabolism and relative plasma and brain levels of pentobarbital. When doxapram was given intraperitoneally 60 min. prior to administration of pentobarbital, doxapram potentiated pentobarbital-induced narcosis in a dose- and time-dependent manner, but had no effect on onset time. Doxapram potentiated hypothermia, increased acute toxicity, and prolonged the pentobarbital half-life in brain and plasma, but measurement of the concentration of pentobarbital in the brain and plasma immediately upon recovery from narcosis showed that there were no differences in any of the groups examined. Also, brain-to-plasma ratios of pentobarbital did not differ between the control and doxapram-treated groups. Doxapram competitively inhibited the hepatic metabolism of pentobarbital in 9000 x g supernatant incubation mixtures. The results obtained from these experiments indicate that inhibition of drug-metabolizing enzymes by doxapram may account for its enhancement of the duration of pentobarbital-induced narcosis.

Animals↗
PubMed1992

Interactive ventilatory effects of two respiratory stimulants, caffeine and doxapram, in newborn lambs.

Caffeine and doxapram are two respiratory stimulants used in the treatment of apnea in newborns. When used concurrently, these drugs may produce interactive effects on the control of breathing in the newborn. The ventilatory effects of these drugs, given alone or together, were measured during 150 min of drug infusion in two groups of awake lambs 2-5 days old. The first group (n = 5) received a caffeine loading dose of 10 mg/kg followed by a maintenance dose of 0.1 mg/kg/h and incremental doses of doxapram: 0.25, 0.5, 1.25 and 2.5 mg/kg/30 min. The second group (n = 5) received a doxapram loading dose of 5.5 mg/kg followed by a maintenance dose of 1 mg/kg/h and incremental doses of caffeine: 2.5, 5.0, 7.5 and 10.0 mg/kg/30 min. In the first group, ventilation increased after the caffeine loading dose from 566 +/- 55 to 680 +/- 74 ml/kg/min (plasma caffeine = 14.7 +/- 1.6 mg/l) and progressively increased with the addition of incremental doses of doxapram up to 1,000 +/- 108 ml/kg/min at 2.5 mg/kg of doxapram (p less than 0.001 compared to baseline and caffeine loading dose). In contrast, in the second group, the doxapram loading dose markedly increased ventilation from 582 +/- 50 to 936 +/- 75 (p less than 0.002 and p less than 0.04 compared to caffeine loading dose) at plasma doxapram of 5.3 +/- 0.8 mg/l, but incremental doses of caffeine had no effects. We conclude that doxapram exerts a brisk and powerful respiratory stimulant effect and produces an additional dose-dependent ventilatory response when added to caffeine.

Animals↗
PubMed1982

Effect of doxapram on the action of other drugs and the hepatic drug-metabolizing system in mice.

Effects of doxapram, a respiratory stimulant, on the action of other drugs and the activity of the hepatic drug-metabolizing enzyme were studied in mice. The hypothermic effect induced by aminopyrine and the muscle relaxant effect induced by meprobamate were potentiated by the pretreatment with doxapram 60 min before. Furthermore, doxapram significantly enhanced the lethalities of picrotoxin and strychnine and the analgesic actions of aminopyrine and morphine. The plasma concentration of aminopyrine or pentobarbital in doxapram-treated mice was higher than those in untreated mice, and the plasma concentration of normustard related to an active metabolite of cyclophosphamide after the administration of cyclophosphamide was lower in doxapram-treated mice. On the other hand, doxapram (50 mg/kg, i.p.) reduced remarkably the activities of aminopyrine N-demethylase and aniline hydroxylase in the hepatic 9,000xg supernatant fraction, and also reduced the cytochrome P-450 contents in hepatic microsomes. However, no significant alteration by doxapram was observed on the activities of NADH-ferricyanide reductase and NADPH-cytochrome c reductase and cytochrome b5 contents. It seems likely that the mechanisms of the interaction between doxapram and combined drugs involved the depression of the hepatic drug-metabolizing system in microsomes and a subsequent variation of drug level in the plasma.

Aminopyrine↗
PubMed1996

Adverse events with continuous doxapram infusion against late postoperative hypoxaemia.

OBJECTIVE: A randomized double-blind controlled trial of doxapram versus placebo against late postoperative hypoxaemia was planned to include 40 patients (2 x 20). RESULTS: After inclusion of 18 patients a serious adverse event was encountered with development of a brain stem infarction in a 90-year-old woman receiving doxapram. At this point the randomization code was broken and we decided to terminate the trial. Three of nine patients receiving doxapram had had an adverse event whereas none of the patients receiving placebo had adverse events (P = 0.2). In the 18 patients studied, there was an insignificant trend towards higher mean oxygen saturation in the doxapram group, and a significantly higher minimum oxygen saturation and reduced number of hypoxaemic events on the first postoperative night. CONCLUSION: Although these preliminary data on the effect of doxapram on postoperative hypoxaemia seem promising, further studies on the effect of continuous nocturnal postoperative doxapram infusion on levels of arterial oxygen saturation should be postponed until more knowledge about the pharmacokinetics of doxapram in this particular clinical situation has been gathered.

Adult↗
PubMed1996

Neuroendocrine responses to laboratory panic: cognitive intervention in the doxapram model.

Doxapram is a respiratory stimulant that appears to be a potent and specific panicogenic agent. It also elicits an abnormal ventilatory response in patients with panic. A replication study confirmed these findings and demonstrated that behavioral and ventilatory responses to doxapram were significantly modified by a psychological intervention designed to cognitively block panic. The replication study provided an opportunity to simultaneously investigate the neuroendocrine effects of the illness, the drug, the drug-induced panic attacks, and the cognitive intervention. Epinephrine (EPI), norepinephrine (NE), growth hormone (GH), adrenocorticotropin (ACTH), and cortisol were studied in patients with panic and control subjects given placebo and doxapram injections after receiving either standard instructions or a brief cognitive intervention. Patients with panic had elevated levels of EPI, ACTH, and cortisol throughout the study. Doxapram had little or no detectable effects on plasma NE, GH, ACTH, and cortisol. Doxapram-induced panic attacks were not associated with elevations in NE, GH, ACTH, or cortisol. Doxapram led to a rapid and very brief rise in plasma EPI, which was small in subjects who did not panic and pronounced in patients who did panic. The cognitive intervention attenuated the EPI response to doxapram, perhaps through its effect on panic, and modified the temporal pattern of ACTH and cortisol secretion. These results suggest that: (1) further study of catecholamine responses within the first few minutes after panic induction is needed; (2) intense panic can occur without significant activation of the hypothalamic-pituitary-adrenal axis; and (3) cognitive factors can modulate neuroendocrine activity in laboratory studies of patients with panic.

Acoustic Stimulation↗
PubMed2005

Doxapram increases corticotropin-releasing factor immunoreactivity and mRNA expression in the rat central nucleus of the amygdala.

Doxapram causes panic anxiety in humans. To determine whether doxapram alters corticotropin-releasing factor (CRF) expression in the central nucleus of the amygdala (CeA), paraventricular nucleus of hypothalamus (PVN), or bed nucleus of the stria terminalis (BNST), we used immunohistochemistry to measure CRF peptide in these brain areas after doxapram injection. Doxapram injection significantly increased CRF-like immunoreactivity (CRF-IR) within the CeA, but not in the BNST or PVN, and this increase was significant 2h after injection. In addition, doxapram significantly increased CRF mRNA expression within the CeA, and this was most prominent 30min after injection. These results suggest that doxapram selectively increases CRF expression within the CeA, and that this is mediated by increased CRF gene transcription. This increase in CRF-IR within the CeA might explain the doxapram-induced anxiety reaction.

Amygdala↗
PubMed2001

QT interval lengthening in premature infants treated with doxapram.

OBJECTIVE: Doxapram, routinely used in premature infants treated for apnea of prematurity unresponsive to methylxanthines, has been related to cardiac conduction disorders. This study was designed to evaluate doxapram cardiac and general tolerance and its relationship to drug plasma concentrations in very premature infants. METHODS: Forty infants (mean +/- SEM, 28.9 +/- 0.3 weeks of gestation) who were given intravenous doxapram, 0.5 to 1 mg/kg per hour, at 15.9 +/- 2.4 days of life were evaluated prospectively. Electrocardiograms were monitored before and during the first 3 days of treatment. QT interval corrected for heart rate (QTc) longer than 440 ms was regarded as clinically pertinent, given that it is considered a significant risk of conduction disorder leading to torsades de pointes and sudden death. Other side effects were recorded. Toxic plasma concentration of doxapram and ketodoxapram was set at >4 mg/L. RESULTS: A statistically significant but moderate lengthening of QTc interval has been observed from 394 +/- 4 ms before doxapram to 409 +/- 4 ms at 48 and 72 hours of treatment (P =.0065). For 6 patients, QTc interval became longer than 440 ms without any other rhythm or conduction disorder. Digestive disorders were observed in 20 infants but 9 presented with concomitant septicemia. No relationship was found between presence or absence of adverse effects and drug plasma concentrations. CONCLUSION: Our study enlightened the lengthening effect of doxapram on QTc interval in premature infants with a risk of exceeding the 440 ms threshold that is considered life-threatening. This finding emphasizes the need for electrocardiogram follow-up when using doxapram in neonates.

Caffeine↗
PubMed1998

Low-dose doxapram for treatment of apnoea following early weaning in very low birthweight infants: a randomized, double-blind study.

The effects of low-dose doxapram (0.5 mg kg(-1)h(-1)) in combination with caffeine were evaluated on apnoea frequency following weaning from mechanical ventilation, and on blood pressure, in very low birthweight (BW) premature infants. Twenty-nine infants with BW < or=1250 g, gestational age at birth (GA) <34 weeks and postnatal age <5 d, who required minimal respiratory support, were included. Following randomization, they received a loading dose of caffeine citrate and a continuous infusion of doxapram (doxapram, n=14) or placebo (n=15) was started. They were extubated 8 h after starting the infusion, which was continued for 5 d. During this period, weaning was well tolerated in both groups, apnoeas occurred less frequently and there was a greater increase in systolic blood pressure in infants treated with doxapram than in controls. Plasma doxapram levels were also higher than expected. It is therefore suggested that doxapram, even at low doses, should not be used during the first few days of life. Careful monitoring of blood pressure is required if doxapram is used later.

Apnea↗
PubMed1992

Effect of doxapram on the rate of recovery from atracurium and vecuronium neuromuscular block.

We have studied the effect of doxapram on the rates of spontaneous and neostigmine-induced recovery from neuromuscular block with atracurium and vecuronium, by measurement of the time to recovery of T1 (first twitch in the train-of-four) from 25 to 75% of control (recovery index, RI). After each neuromuscular blocking drug, RI was measured without administering either doxapram or neostigmine (control group), or after administration of doxapram 1 mg kg-1, neostigmine 50 micrograms kg-1 or a combination of doxapram and neostigmine, in groups of 10 patients. RI was significantly longer after vecuronium in the presence of doxapram compared with control (20.1 min vs 14.6 min). There was no significant difference in the RI after atracurium in the presence of doxapram compared with control (12.5 min vs 11.8 min) or when neostigmine was administered with or without doxapram (2.4 min vs 2.4 min, respectively after vecuronium; 3.3 min vs 2.9 min, respectively, after atracurium).

Adolescent↗
PubMed1999

Severe side effects and drug plasma concentrations in preterm infants treated with doxapram.

A high-performance liquid chromatography method has been developed for simultaneous determination of doxapram and its metabolites including ketodoxapram, the main and only active metabolite. The aim of the study was to evaluate this microtechnique and to report the cases involving severe adverse effects to determine toxic plasma levels in neonates. The method was found to be selective, and showed a good baseline separation of doxapram and metabolites. Recovery, linearity, intraday/interday precision, and limit of detection determined in aqueous solutions and in spiked plasma were satisfactory. The assay is simple, rapid, and plasma-sparing, which represents a true advantage in managing neonates. Case analysis was performed in two consecutive periods: 124 preterm infants in the first period and 173 in the second period. Severe toxic effects were observed in 4 cases in the first period, with doxapram plus keto-doxapram levels 9 mg/L. In the second period, only one case was observed. High-range plasma concentrations were significantly less frequent in the second period than in the first one. The authors conclude that measuring doxapram plus keto-doxapram in plasma may be of interest to avoid severe toxic effects in preterm neonates treated with doxapram.

Chromatography, High Pressure Liquid↗
PubMed1993

Doxapram improves pulmonary function after upper abdominal surgery.

The effects of doxapram on postoperative pulmonary function were studied in 40 ASA I and II patients randomly allocated to receive either doxapram 1.8 mg.kg-1.h-1 or placebo for 2 h immediately after elective cholecystectomy. The two groups displayed similar reductions of carbon dioxide production at 2 h and 6 h postoperatively, whereas oxygen consumption remained at preoperative levels for 24 h. Minute ventilation was similarly reduced in the two groups at 2 h and 6 h postoperatively, with corresponding increases in PaCO2. PaO2 was similarly and significantly decreased in both groups postoperatively, whereas P(A-a)O2 remained unchanged at 2 h and 6 h in doxapram-treated patients. FRC was reduced postoperatively in both groups, significantly more so in the control group at 6 h. Various indices of intrapulmonary gas distribution, including the functional (nitrogen) dead space, underwent similar changes in the two groups. By contrast, the physiological dead space was reduced in doxapram-treated patients at 2 h, 6 h and 24 h postoperatively, whereas no significant changes were seen in the control group. The ventilatory equivalent for CO2 was significantly lower in the doxapram-treated group, implying higher ventilatory efficiency. Our findings indicate that infusion of doxapram postoperatively attenuates the impairment of pulmonary function postoperatively, chiefly via effects on V'A/Q' ratios. No side effects of doxapram were observed.

Abdomen↗
PubMed1996

The influence of alfentanil pre-treatment on ventilatory effects of doxapram following induction of anaesthesia with propofol.

BACKGROUND: Hypoventilation may occur following induction of anaesthesia with propofol and is potentiated by concurrent use of opioid drugs. This effect is undesirable in patients who will continue to maintain spontaneous respiration during anaesthesia and surgery. The analeptic drug doxapram is known to have selective respiratory stimulatory effects but its action during induction of anaesthesia has been inconsistent. METHOD: In a double-blind, placebo-controlled study, the influence of alfentanil pre-treatment on the ventilatory effects of doxapram given during induction of anaesthesia with propofol was studied in 40 patients. Four groups of ten patients (two groups pre-treated with 7 micrograms.kg-1 of alfentanil and two groups with saline) were randomly allocated to receive either 0.5 mg.kg-1 doxapram or saline following infusion of propofol to loss of verbal contact. RESULTS: In the groups that received doxapram, minute volumes were significantly increased and end-tidal carbon dioxide concentrations were significantly reduced compared to control groups, although the duration and extent of these effects were less in the group that received alfentanil. Doxapram also reversed an alfentanil-induced reduction in respiratory rate. No adverse cardiovascular or neurological stimulatory effects of doxapram were evident at any time. CONCLUSION: We conclude that doxapram 0.5 mg.kg-1 is effective in augmenting ventilation that has been obtunded following induction of anaesthesia with propofol in patients pre-treated with alfentanil.

Adolescent↗
PubMed1996

Metabolic, ventilatory and circulatory effects of doxapram in anaesthetized pigs during normoxia and hypoxia.

BACKGROUND: In a previous clinical study doxapram was found to improve ventilatory efficacy postoperatively, presumably via effects on hypoxic pulmonary vasoconstriction (HPV). The present study was designed to see whether doxapram induced any changes of arterial oxygenation and pulmonary vascular resistance during normoxia or hypoxia and whether the changes were influenced by the anaesthetic agents. METHODS: Seventeen piglets were anaesthetized by combinations of either midazolam + fentanyl + pancuronium + pentobarbital (TIVA, n = 9), or by midazolam + fentanyl + pancuronium + halothane, 0.5% in end-tidal gas (Hal, n = 8). Analyses of expired gas and mixed venous and arterial blood in combination with determinations of central blood flow and pressures allowed for calculations of standard metabolic, ventilatory and circulatory data. Values were obtained at normoventilation using normoxic (FIO2 = 0.3) and hypoxic (FIO2 = 0.08) gas mixtures at calculated doxapram plasma concentrations of 1, 2 and 4 micrograms.ml-1. RESULTS: With few exceptions doxapram administration affected the investigated variables only moderately during normoxia. In group Hal, PVR and SVR showed a biphasic raise (P < 0.05), CO fell (P < 0.05-P > or = 0.05) and C (a-v)O2 rose (P < 0.05). In group TIVA, PaO2 fell (P < 0.01-0.05) despite unchanged PVR, CO and VD/VT. Hypoxia affected a moderate increase in PVR in group TIVA (P < 0.05), which was slightly lower at the lowest and highest plasma levels of doxapram (P < 0.05). In group Hal, the induction of hypoxia induced a more pronounced rise in PVR (P < 0.05) which showed a biphasic response to increasing dose levels of doxapram, the lowest dose affecting a further rise (P < 0.05) and the highest a reduction to values below hypoxia control levels (P < 0.05). Pronounced differences between the two groups with respect to values for metabolic and circulatory variables make the interpretation of data difficult. CONCLUSIONS: Doxapram administration to anaesthetized animals did not induce any effects indicative of augmentation of the HPV response.

Anesthesia↗
PubMed1996

Use of the respiratory stimulant doxapram in southern elephant seals (Mirounga leonina).

The use of doxapram to stimulate breathing was examined in southern elephant seals chemically restrained with ketamine and xylazine. Animals which were breathing spontaneously received doxapram (approximately 0.5, 1, 2, or 4 mg/kg) or saline into the extradural intravertebral vein. Doxapram caused a dose-dependent increase in the depth and rate of respiration which began within one minute, peaked after two minutes and lasted for up to five minutes. A dose of 2 mg/kg appeared to be safe and effective for the stimulation of respiration, while 4 mg/kg caused arousal and shaking. Doxapram (2 mg/kg) was tested on 14 occasions in animals which had developed apnoea during chemical restraint. Doxapram had no effect when administered into the extradural intravertebral vein and appeared to be of more benefit when administered directly into the lungs via an endotracheal tube, but it was not effective in all cases. There was evidence to suggest that the endotracheal tube prevented some of the animals from breathing. The effect of intubation and endotracheal doxapram administration was therefore examined in 19 apnoeic and 31 spontaneously breathing seals. Intubation induced apnoea in animals at low levels of chemical restraint and endotracheal doxapram was unreliable for the stimulation of breathing.

Animals↗