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Doxapram (Doxapram Hydrochloride) - Summary



Doxapram Hydrochloride Injection USP, is a clear, colorless, sterile, non-pyrogenic, aqueous solution with pH 3.5 to 5, for intravenous administration. Each mL contains doxapram hydrochloride 20 mg, benzyl alcohol (as preservative) 0.9%, and water for injection, q. s. Due to its benzyl alcohol content, doxapram hydrochloride injection should not be used in newborns. Doxapram is a respiratory stimulant. Doxapram hydrochloride is a white to off-white, crystalline powder, sparingly soluble in water, alcohol and chloroform.


a. When the possibility of airway obstruction and/or hypoxia have been eliminated, doxapram may be used to stimulate respiration in patients with drug-induced postanesthesia respiratory depression or apnea other than that due to muscle relaxant drugs.

b. To pharmacologically stimulate deep breathing in the postoperative patient. (A quantitative method of assessing oxygenation, such as pulse oximetry, is recommended.)

Drug-induced central nervous system depression.

Exercising care to prevent vomiting and aspiration, doxapram may be used to stimulate respiration, hasten arousal, and to encourage the return of laryngopharyngeal reflexes in patients with mild to moderate respiratory and CNS depression due to drug overdosage.

Chronic pulmonary disease associated with acute hypercapnia.

Doxapram is indicated as a temporary measure in hospitalized patients with acute respiratory insufficiency superimposed on chronic obstructive pulmonary disease. Its use should be for a short period of time (see DOSAGE AND ADMINISTRATION) as an aid in the prevention of elevation of arterial CO2 tension during the administration of oxygen.

It should not be used in conjunction with mechanical ventilation.

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Published Studies Related to Doxapram

Respiratory and cardiovascular effects of doxapram and theophylline for the treatment of asphyxia in neonatal calves. [2010.03.15]
Respiratory stimulants are widely used in asphyxic neonatal calves despite a lack of data about their effectiveness and indications of possible side effects. The effect of doxapram and theophylline on respiratory, cardiovascular, and acid-base variables was investigated in 10 healthy neonatal calves (Bos Taurus).

Comparative study on effectiveness of doxapram and pethidine for postanaesthetic shivering. [2009.04]
INTRODUCTION: Postanaesthetic shivering is a common condition after surgery which needs proper management with pharmacologic agents so as to make postoperative period comfortable to the patient and prevent from the untoward complications that can arise from it. This study was done to compare the effectiveness of Pethidine and Doxapram in the treatment of postanaesthetic shivering... CONCLUSIONS: Pethidine was found to be more effective compared to Doxapram in treating patients with postoperative shivering.

The effect of doxapram on brain imaging in patients with panic disorder. [2007.10]
Administration of doxapram hydrochloride, a respiratory stimulant, is experienced by panic disorder patients to be similar to panic attacks but has reduced emotional effect in normal volunteers, thus providing a laboratory model of panic for functional imaging... This suggests that panic disorder patients activate frontal inhibitory centers less than controls, a tendency that may lower the threshold for panic.

Doxapram shortens recovery following sevoflurane anesthesia. [2006.05]
PURPOSE: A randomized, double blind controlled trial was undertaken to investigate the effect of doxapram on recovery times and bispectral index following sevoflurane anesthesia... CONCLUSION: We conclude that doxapram 1 mg.kg(-1) hastens early recovery from sevoflurane anesthesia, and this arousal effect correlates with higher bispectral index values.

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Clinical Trials Related to Doxapram

Doxapram as an Additive to Propofol Sedation in Sedation for ERCP [Not yet recruiting]
Sedation is needed in order to complete endoscopic retrograde cholangiopancreatography (ERCP) to alleviate discomfort and pain during the procedure. This is usually achieved with use of opioids and/or sedative agents such as benzodiazepines or propofol. Traditionally benzodiazepines have been used but nowadays propofol is becoming the drug of choice for sedation during ERCP. The problem with propofol sedation is the fact that it may case cardiorespiratory depression and there is no antidote for this like there is for benzodiazepines. Cardiovascular depression can usually be easily counteracted with drugs that are used to raise blood pressure or heart rate during general anesthesia but respiratory depression remains a problem. The aim of this study is to try to counteract the respiratory depression caused by propofol sedation using an old respiratory stimulant doxapram as opposed to placebo using a double blind randomized protocol. The investigators hypothesis is that boluses and an infusion of doxapram will alleviate the respiratory depression caused by propofol sedation.

Dosing Chart for Calculating the First Dose of Doxapram in Premature Infants [Completed]
Doxapram is used to stimulate respiration. For a given dose, the fluctuations in concentrations observed in infants' blood may be wide, leading to a risk of lack of efficacy or of toxic effects. Two factors are linked to these fluctuations: age and gender. The aim of this study is to compare a dosage regimen based only on patient's weight, to another one using a dosing chart taking into account weight, age and gender.

Aminophylline and Cognitive Function After Sevoflurane Anaesthesia [Completed]
Early postoperative recovery of neurologic and cognitive functions is especially advantageous after fast-tracking ambulatory procedures to hasten home discharge after surgery. 1 It is well known that volatile anaesthetic agents may generate adverse postoperative cognitive effects and even traces of it may affect task performance in healthy volunteers. 2Hence, rapid elimination of the volatile anaesthetics may help reduce postoperative confusion and cognitive impairment in surgical patients by facilitating a faster recovery from general anaesthesia. 3 Sevoflurane has been advocated for the routine anesthesia for ambulatory surgery patients. It activates adenosine A1 receptors in primary rat hippocampal cultures through the liberation of adenosine secondary to the interaction of with adenosine transport or key enzymes in adenosine metabolism. 4 However; sevoflurane anaesthesia is associated with slower emergence and delayed early postoperative cognitive recovery than desflurane5 and xenon2 anaesthesia. Aminophylline, which is a hydrophilic cyclic adenosine mono-phosphate (cAMP) dependent phosphodiesterase inhibitor has been used for long time to antagonize the sedative effects of morphine, diazepam, and barbiturates. 6-7Aminophylline in doses of 2-5 mg/kg shortens the recovery from sevoflurane anaesthesia and improves bispectral index scores (BIS) with concurrent increases in heart rate which might have a detrimental effect in patients with ischaemic heart disease. 8-11However, the use of smaller doses of 2-3 mg/kg is associated with less increases in heart rate. 10-11 The use of 1 mg/kg of Doxapram is comparable to 2 mg/kg of aminophylline in improvement of early recovery from sevoflurane anaesthesia secondary to its central nervous system stimulating effect rather than increased ventilatory elimination of sevoflurane. 11 Currently, there is no available published studies have investigated the effects of either theophylline or doxapram on early postoperative cognitive recovery after balanced anaesthesia with sevoflurane. We hypothesized that the use of small doses of aminophylline [2-3 mg/kg] may be comparable to larger doses in improvement of the early postoperative cognitive recovery from sevoflurane anaesthesia with associated non-significant increases in heart rate. The present study investigated the effects of 1 mg/kg of doxapram, and 2, 3, 4, and 5 mg/kg of aminophylline on the early postoperative cognitive recovery using the Short Orientation Memory Concentration Test (SOMCT), response entropy (RE) state entropy (SE), difference between RE and SE (RE-SE), end-tidal sevoflurane concentration, haemodynamics, the times to eyes opening and to extubation and degree of sedation after sevoflurane anaesthesia in patients undergoing ambulatory surgery.

Population PK/PD of Off Label Drugs in Premature Neonates [Recruiting]
This study will provide information on the pharmacokinetics, safety and effectiveness of off--label drugs used in critically ill premature infants: doxapram, fentanyl, midazolam, paracetamol, phenobarbital, sildenafil, levetiracetam and fluconazole. PK/PD analysis with NONMEM (non-linear mixed effects modelling) will result in (adapted) dosage guidelines, thus contributing towards an improvement in the quality of care and cost efficiency. Furthermore the development of Dried Blood Spot (DBS) analysis is investigated for these drugs as a minimally invasive method for conventional patient care and to perform pharmacological studies in children. The adapted dosage guidelines will be implemented directly into clinical practice in collaboration with the NKFK. Therefore the study is designed as an observational multicenter study to be able to collect sufficient data for the drugs of interest.

The Effect of Stimulating Substances on Brain Activity of Preterm Infants [Recruiting]
Introduction: Methylxanthines and doxapram have been widely used for the treatment of apneas of prematurity. Both substances have effects on the central nervous system. While there are data available concerning the use of caffeine (the methylxanthine used at our NICU) even proposing a positive effect on neurodevelopmental outcome of very preterm infants, there are data which suggest a negative effect of the central stimulants doxapram on longterm outcome in this group of infants. Nevertheless concerning both medications only few studies have been published and only scarce data are available concerning the effect of these medications on brain activity of very preterm infants until now. The aim of this study: is the assessment of the effect of stimulating substances on brain activity of preterm infants born below 30 weeks of gestation and their longterm neurodevelopmental follow-up. Methods: This study is a prospective study including preterm infants born below 30 weeks of gestational age. Brain activity is measured by one-channel amplitude-integrated EEG (aEEG). The first aEEG measurement is performed without caffeine and/or doxapram medication. At least one hour of brain activity is registrated. The second measurement is done at least 24 hours after the start of caffeine and/ or doxapram treatment. The percentage of different background patterns, the occurrence and duration of sleep-wake-cycling, and the occurrence and duration of seizures is assessed and analysed. Neurodevelopmental outcome is assessed at one and two years of corrected age by assessment of the Bayley Scales of Infant Development II and standardized clinical neurological examination.

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Page last updated: 2010-10-05

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