The effects of doxapram on haematology, serum biochemical parameters and erythrocyte oxidant/ antioxidant status in dogs anaesthetized with propofol.

The present prospective randomized experimental study was designed to determine the effects of doxapram on haematological, serum biochemical and antioxidant status in dogs after propofol anaesthesia. Twenty-four healthy male mixed breed dogs, aged 1-2 years, weighing 20.4 ± 2.6 kg was studied. Each dog was anaesthetized twice, with at least one week for washout. Animals were sedated with acepromazine (0.1 mg/kg) intramuscularly. Forty minutes later, anaesthesia was induced using intravenous (IV) propofol (4 mg/kg) titration and maintained for 30 min by propofol (0.2 mg kg-1  min-1 ). After propofol was discontinued, doxapram (2 mg/kg) hydrochloride was administrated IV in PD treatment while an equal volume of saline was administrated in PS treatment. Blood parameters were analysed in four times: immediately before sedation (T1), after treatment (T2), after complete recovery (T3) and 24 hr later (T4). Haematological assessments revealed no significant difference between treatments except in haematocrit which was significantly reduced at T4 (24 hr later) in PD. A decreasing trend of all haematological variables was observed after doxapram administration until recovery, except monocyte, mean corpuscular haemoglobin, red blood cell distribution width and platelet count. Serum urea, creatinine, glucose, cholesterol, direct bilirubin concentration and alanine aminotransferase activity were not changed following doxapram administration compared to the PS treatment. After doxapram administration, Creatinine (T3), Albumin (T2) and Protein (T2 & T3) decreased while Glucose (T2 & T3) and BT (T3) increased. Antioxidant parameters measured showed no difference between treatments or time. Doxapram (2 mg/kg) IV did not induce any major negative effects on haematological, serum biochemical variables and oxidant/antioxidant status in dogs after propofol anaesthesia.

Intravenous doxapram administration as a potential model of panic attacks in rats.

Panic disorder can be categorized into the nonrespiratory or the respiratory subtypes, the latter comprising dyspnea, shortness of breath, chest pain, feelings of suffocation, and paresthesias. Doxapram is an analeptic capable of inducing panic attacks with respiratory symptoms in individuals diagnosed with the disorder; however, its neuroanatomical targets and its effects on experimental animals remain uncharacterized. One of the brain regions proposed to trigger panic attacks is the midbrain periaqueductal gray (PAG). Therefore, in this study, we evaluated the effects of doxapram in Fos (c-Fos) protein expression in the PAG and characterized its cardiorespiratory and behavioral effects on the elevated T maze and in the conditioned place aversion (CPA) paradigms. Doxapram increased Fos expression in different columns of the PAG, increased respiratory frequency, decreased heart rate, and increased arterial pressure when injected via intravenous route. Alprazolam, a panicolytic benzodiazepine, injected via intraperitoneal route, decreased respiratory frequency, whereas URB597, an anandamide hydrolysis inhibitor injected via intraperitoneal route, was ineffective. Doxapram injected via intraperitoneal route induced an anxiogenic-like effect in the elevated T-maze model; however, it failed to induce CPA. This study suggests that the cardiorespiratory and behavioral effects of doxapram in rodents serve as an experimental model that can provide insights into the neurobiology of panic attacks.

Doxapram alleviates low SpO2 induced by the combination of propofol and fentanyl during painless gastrointestinal endoscopy.

BACKGROUND: Painless gastrointestinal endoscopy under intravenous propofol anesthesia is widely applied in the clinical scenario. Despite the good sedation and elimination of anxiety that propofol provides, low SpO2 may also result. Doxapram is a respiratory stimulant with a short half-life. The primary aim of this study was to investigate the effects of doxapram on alleviating low SpO2 induced by the combination of propofol and fentanyl during painless gastrointestinal endoscopy. METHODS: In this prospective study, patients scheduled for painless gastrointestinal endoscopy were randomly assigned to group D or S with 55 patients per group. Initially, both groups received a combination of propofol and fentanyl. Patients in group D received 50 mg doxapram after propofol injection, while patients in group S received an equal volume of saline. Vital signs of the patients, propofol dose, examination duration, and incidences of low SpO2 were recorded. RESULTS: There were no statistical differences in propofol consumption and examination duration between the two groups. Twenty-six patients in group S experienced low SpO2 versus 10 in group D (P = 0.001). Nineteen patients in group S underwent oxygenation with a face mask in contrast to 8 in group D (P = 0.015). Eighteen patients in group S were treated with jaw lifting compared to 5 in group D (P = 0.002). Four patients in group S underwent assisted respiration compared to 2 in group D (without statistical difference). The average oxygen saturation in group S was significantly lower than that in group D at 1, 2 and 3 min after propofol injection (P < 0.001, P = 0.001 and P = 0.020, respectively). There were no statistical differences in oxygen saturation at other time points. There were no statistical differences in MAP and HR (except for the time point of 1 min after the induction) between the two groups. CONCLUSIONS: Low dose of doxapram can effectively alleviate low SpO2 in painless gastrointestinal endoscopy with intravenous propofol, without affecting propofol consumption, examination duration, MAP, or HR. TRAIL REGISTRATION: The study was approved by the Institutional Ethics Committee of Clinical and New Technology of Wuxi People's Hospital on 20th July, 2018 (KYLLH2018029) and registered in the Chinese Clinical Trial Register on 16th August, 2018 (ChiCTR1800017832).

Doxapram Treatment and Diaphragmatic Activity in Preterm Infants.

BACKGROUND: Doxapram is a treatment option for severe apnea of prematurity (AOP). However, the effect of doxapram on the diaphragm, the main respiratory muscle, is not known. OBJECTIVES: To investigate the effect of doxapram on diaphragmatic activity measured with transcutaneous electromyography of the diaphragm (dEMG). METHODS: A pilot study was conducted in a tertiary neonatal intensive care unit. Diaphragmatic activity was measured from 30 min before up to 3 h after the start of doxapram treatment. dEMG parameters were compared to baseline (5 min before doxapram treatment) and at 15, 60, 120 and 180 min after the start of doxapram infusion. RESULTS: Eleven preterm infants were included with a mean gestational age of 25.5 ± 1.2 weeks and birth weight of 831 ± 129 g. The amplitudedEMG, peakdEMG and tonicdEMG values did not change in the 3 h after the start of doxapram infusion compared to baseline. Clinically, the number of apnea episodes in the 24 h after doxapram treatment decreased significantly. CONCLUSION: Doxapram infusion does not alter diaphragmatic activity measured with transcutaneous dEMG in preterm infants with AOP, indicating that its working mechanism is primarily on respiratory drive and not on respiratory muscle activity.

Comparison of the effects of alfaxalone and propofol with acepromazine, butorphanol and/or doxapram on laryngeal motion and quality of examination in dogs.

OBJECTIVE: To compare the effects of alfaxalone and propofol, with and without acepromazine and butorphanol followed by doxapram, on laryngeal motion and quality of laryngeal examination in dogs. STUDY DESIGN: Randomized, crossover, blinded study. ANIMALS: Ten female Beagle dogs, aged 11-13 months and weighing 7.2-8.6 kg. METHODS: The dogs were administered four intravenous (IV) treatments: alfaxalone (ALF), alfaxalone+acepromazine and butorphanol (ALF-AB), propofol (PRO) and propofol+AB (PRO-AB). AB doses were standardized. Dogs were anesthetized 5 minutes later by administration of alfaxalone or propofol IV to effect. Arytenoid motion during maximal inspiration and expiration was captured on video before and after IV doxapram (0.25 mg kg-1). The change in rima glottidis surface area (RGSA) was calculated to measure arytenoid motion. An investigator blinded to the treatment scored laryngeal examination quality. RESULTS: A 20% increase in RGSA was the minimal arytenoid motion that was detectable. RGSA was significantly less in ALF before doxapram compared with all other treatments. A <20% increase in RGSA was measured in eight of 10 dogs in PRO and in all dogs in ALF before doxapram. After doxapram, RGSA was significantly increased for PRO and ALF; however, 20% of dogs in PRO and 50% of dogs in ALF still had <20% increase in RGSA. A <20% increase in RGSA was measured in five of 10 dogs in PRO-AB and ALF-AB before doxapram. All dogs in PRO-AB and ALF-AB with <20% increase in RGSA before doxapram had ≥20% increase in RGSA after doxapram. Examination quality was significantly better in PRO-AB and ALF-AB. CONCLUSIONS AND CLINICAL RELEVANCE: The use of acepromazine and butorphanol improved the quality of laryngeal examination. Any negative impact on arytenoid motion caused by these premedications was overcome with doxapram. Using either propofol or alfaxalone alone is not recommended for the evaluation of arytenoid motion.

Doxapram Treatment for Apnea of Prematurity: A Systematic Review.

BACKGROUND: Apnea of prematurity (AOP) is a common complication of preterm birth, for which caffeine is the first treatment of choice. In case of persistent AOP, doxapram has been advocated as an additional therapy. OBJECTIVE: To identify and appraise all existing evidence regarding efficacy and safety of doxapram use for AOP in infants born before 34 weeks of gestational age. METHODS: All studies reporting on doxapram use for AOP were identified by searching electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research. Two reviewers independently assessed study eligibility and quality, and extracted data on study design, patient characteristics, efficacy and safety outcomes. RESULTS: The randomized controlled trials showed less apnea during doxapram treatment when compared to placebo, but no difference in treatment effect when compared to theophylline. No serious adverse effects were reported. We identified 28 observational studies consisting mainly of cohort studies and case series (n = 1,994). There was considerable heterogeneity in study design and quality. Most studies reported a positive effect of doxapram on apnea rate. A few studies reported on long-term outcomes with conflicting results. A range of possible doxapram-related short-term adverse effects were reported, sometimes associated with the use of higher doses. CONCLUSION: Based on the limited number of studies and level of evidence, no firm conclusions on the efficacy and safety of doxapram in preterm infants can be drawn. For this reason, routine use cannot be recommended. A large multicenter randomized controlled trial is urgently needed to provide more conclusive evidence.

Doxapram-mediated Increase in Cardiac Output Reduces Opioid Plasma Concentrations: A Pharmacokinetic/Pharmacodynamic-Pharmacokinetic/Pharmacodynamic Modeling Study in Healthy Volunteers.

Doxapram is an analeptic that induces ventilatory stimulation and increases blood pressure and cardiac output (CO). Its mechanism of action is the blockade of background K+ -channels expressed on type 1 carotid body cells. In the randomized controlled trial, the authors explored the role of the increase in CO by doxapram (plasma concentration (Cp) 1,000-3,500 ng/mL) on the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the potent opioid alfentanil (Cp 100-200 ng/mL). Population PK-PD analyses were performed on the doxapram PK-CO data and the alfentanil PK-antinociception data. The analyses showed that the doxapram-induced increase in CO explained the increase in alfentanil distribution and elimination clearances causing a significant reduction in plasma alfentanil Cp and antinociception. This novel approach in which one PK-PD model effectively drives another PK-PD model highlights the importance of physiological influences on PK and PD of a potent opioid with rapid onset of effect and low clinical margin of safety.

Doxapram Dosing for Apnea of Prematurity Based on Postmenstrual Age and Gender: A Randomized Controlled Trial.

INTRODUCTION: Doxapram is used as a third-line treatment for apnea unresponsive to caffeine and continuous positive airway pressure (CPAP) in preterm infants. OBJECTIVES: The objectives of this study were to compare the effects of dosing adjusted for gender and postmenstrual age (PMA) (GrA) versus infants' weight alone (GrW) on doxapram plasma levels, clinical efficacy, and side effects. METHODS: This was a randomized, double-blind study, including premature infants for whom optimized caffeine and CPAP therapy for apnea of prematurity had failed. Failure was defined as the persistence of more than one significant apnea per hour over an 8-h period. Plasma levels of doxapram and ketodoxapram were measured with high-performance liquid chromatography (HPLC) 48 h after the onset of treatment. Dosing aimed to maintain the combined doxapram and ketodoxapram plasma level in the therapeutic range of 1.5-4 mg/l. Infants were followed-up for 4 days after the onset of treatment. RESULTS: A total of 85 infants were included: 46 in GrW (27.7 ± 1.9 weeks' gestational age [GA]), 39 in GrA (27.9 ± 1.4 weeks' GA); available plasma levels showed that 25 of 40 in the GrW group and 27 of 37 in the GrA group had levels within the therapeutic range (p = 0.344). Of note, plasma level variance was significantly higher in GrW for doxapram + ketodoxapram (1.87 vs. 0.89; p = 0.028). Clinical efficacy was better in the GrA group, with a reduction from 32 to 3 of 38 (76 %) infants with significant apnea versus 30 to 5 of 45 (56 %) in the GrW group (p < 0.001). No adverse effects were observed during the study. CONCLUSIONS: Taking gender and PMA into account for doxapram dosing did not significantly increase the number of infants with a plasma level in the therapeutic range. However, it improved plasma level stability and clinical efficacy without adverse effects. ClinicalTrials.gov number: NCT00389909.

An Impedance-Based Model for the Assessment of Cardiopulmonary Function in Rabbits.

Improving the quality of physiologic data collected from research animals is most easily accomplished by collecting as much information as possible from a single subject, thereby reducing animal use and error associated with satellite groups. We investigated the feasibility of using a large-animal implantable telemetry device in New Zealand white rabbits (n = 6). The first task was to develop an implantation technique that yielded calibrated tidal volume (Vt) measurements that were within 10% of those obtained simultaneously from a pneumotachograph, a low-noise electrocardiogram, and stable blood pressure. The second task was to challenge implanted rabbits with the respiratory stimulant doxapram to assess linearity of the calibration across a range of Vt. Of the 3 electrode placements attempted, only one resulted in calibrations consistently below 10% error. Optimal electrode placement resulted in calibrated Vt measurements within 1.7% ± 0.3% of those obtained from a pneumotachograph during normal tidal breathing, 7.3% ± 0.7% of those after saline injection, and 6.0% ± 0.5% of those after doxapram injection. The Vt range was 9 to 15 mL for normal tidal breathing and saline injection and 25 to 30 mL after doxapram injection. Increases in mean arterial pressure of 25.0 ± 6.82 mm Hg and decreases in heart rate of 56.3 ± 6.82 bpm were associated with doxapram injection only. Our findings represent the first time that multiple cardiopulmonary endpoints have been assessed by telemetry in conscious, restrained rabbits. Whether animal position affects calibration accuracy warrants investigation.

Long-Term Neurodevelopmental Outcome after Doxapram for Apnea of Prematurity.

BACKGROUND: Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP). OBJECTIVE: To evaluate the effect of doxapram on long-term neurodevelopmental outcome in preterm infants as its safety still needs to be established. METHODS: From a retrospective cohort of preterm infants with a gestational age (GA) <30 weeks and/or a birth weight <1,250 g, born between 2000 and 2010, infants treated with doxapram (n = 142) and a nontreated control group were selected (n = 284). Patient characteristics and clinical and neurodevelopmental outcome data at 24 months' corrected age were collected. Neurodevelopmental delay (ND) was defined as having a Mental or Psychomotor Developmental Index (MDI/PDI) <-1 standard deviation (SD), cerebral palsy, or a hearing or visual impairment. Odds ratios (OR) were calculated using multiple logistic regression analyses adjusting for potential confounders. RESULTS: Infants treated with doxapram had a lower GA compared to controls. The number of infants with a MDI or PDI <-1 SD was not different between the groups. The risk of the combined outcome death or ND was significantly lower in the doxapram group after adjusting for confounding factors (OR = 0.54, 95% CI: 0.37, 0.78). Doxapram-treated infants had a higher risk of bronchopulmonary dysplasia and patent ductus arteriosus, but a lower risk of spontaneous intestinal perforation. All other morbidities were not different between the groups. CONCLUSIONS: This study suggests that doxapram is not associated with an increased risk of ND. These findings need to be confirmed or refuted by a large, well-designed, placebo-controlled randomized trial.

Repeated intravenous doxapram induces phrenic motor facilitation.

Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6mg/kg) or as a series of 3 injections (2mg/kg) at 5min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2mg/kg. At 60min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (P<0.05 vs. controls), but was 103±8%BL and 112±4%BL in the groups receiving a single dose of 2 or 6mg/kg, respectively. Following bilateral section of the carotid sinus nerves, the acute phrenic response to doxapram (2mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury.

Refinement of the dose of doxapram to counteract the sedative effects of acepromazine in dogs.

OBJECTIVES: To evaluate the effectiveness of two doses of doxapram in reversing acepromazine sedation in dogs. METHODS: Using a crossover design, 10 adult mixed-breed dogs received 0·05 mg/kg acepromazine, intramuscularly (im) followed 30 minutes later by one of the three randomly determined treatments: 0·0625 mL/kg saline, intravenously (iv), 1·25 mg/kg doxapram, iv or 2·5 mg/kg doxapram, iv. Sedation scores were obtained by a single, blinded observer at 0, 15 and 30 minutes after acepromazine administration and at 5, 15 and 30 minutes after the treatment administration. RESULTS: The mean baseline sedation score of all the treatments was not different among treatments. All the dogs had a significant increase in sedation score at 30 minutes after acepromazine administration. Both the low and high doses of doxapram showed a significant decrease in sedation score compared to saline, but there was no significant difference between the two doses. Five dogs in the high dose group panted after treatment injection, and this was significantly more than in the low dose group. CLINICAL SIGNIFICANCE: Doxapram is effective in reducing the sedative effects of acepromazine over a short period of time. A dose of 1·25 mg/kg effectively decreases acepromazine sedation without causing panting.

Effects of obesity on lung function and airway reactivity in healthy dogs.

The present study investigated the effects of bodyweight (BW) gain on respiratory function and airway responsiveness in healthy Beagles using barometric whole body plethysmography (BWBP). Six adult dogs were examined before and after a fattening diet. The high-energy diet induced a mean increase in BW of 41±6%. BWBP basal parameters were recorded prior to airway reactivity testing (using increasing concentrations of histamine nebulisations). An airway responsiveness index (H-Penh300) was calculated as the histamine concentration necessary to reach 300% of basal enhanced pause (Penh, bronchoconstriction index). The same dogs underwent a doxapram hydrochloride (Dxp) stimulation testing 2 weeks later. Basal measurements showed that obese dogs had tidal volume per kg (TV/BW) that was significantly decreased whilst respiratory rate (RR) increased significantly. H-Penh300 decreased significantly in obese Beagles, indicating increased bronchoreactivity. Dxp administration induced a significant increase in TV/BW, minute volume per kg (MV/BW), peak inspiratory and expiratory flows per kg (PIF/BW and PEF/BW) in both normal and obese dogs although the TV/BW increase was significantly less marked in the obese group. In conclusion, obesity induced changes in basal respiratory parameters, increased bronchoreactivity and a blunted response to Dxp-induced respiratory stimulation. This combination of basal respiratory parameters, bronchoreactivity testing and pharmacological stimulation testing using non-invasive BWBP can help characterize pulmonary function and airway responsiveness in obese dogs.

Emergence agitation in adults: risk factors in 2,000 patients.

PURPOSE: The study was designed to determine the incidence of postoperative agitation following general anesthesia in 2,000 adult patients and to examine the associated risk factors. METHODS: The study enrolled 2,000 adults who were scheduled for surgery under general anesthesia in a single institution during December 2007 to December 2008. The following risk factors were examined: age, gender, ASA physical status, type of surgery, anesthesia technique (inhalational or intravenous), administration of neostigmine or doxapram, adequate postoperative analgesia, pain, presence of a tracheal tube, and presence of a urinary catheter. RESULTS: Agitation occurred in 426 patients (21.3%). It was more common in males (28.1%) than in females (16.1%) (P = 0.017) and more prevalent after inhalational (27.8%) than total intravenous (7.5%) anesthesia (P = 0.001). Agitation was more common after oral cavity and otolaryngological surgery than after other types of surgery. Multivariate analysis showed that use of doxapram (odds ratio [OR] = 9.2; 95% confidence interval [CI] = 6.2 - 15.4; P = 0.002) and pain (OR = 8.2; 95% CI = 4.5 - 16.9; P < 0.001) were the most important risk factors associated with emergence agitation. Other causes were the presence of a tracheal tube and/or a urinary catheter. Adequate postoperative analgesia was associated with less agitation (OR = 0.4; 95% CI = 0.1 - 0.4; P = 0.006). CONCLUSION: Doxapram administration, pain, and presence of a tracheal tube and/or a urinary catheter appear to be the most important causes of postoperative agitation. To avoid this complication, it is suggested, whenever possible, to use intravenous anesthesia, to remove endotracheal tubes and urinary catheters as early as possible, and to provide adequate postoperative analgesia.

Respiratory inductive plethysmography as a method for measuring ventilatory parameters in conscious, non-restrained dogs.

INTRODUCTION: Assessing the effects of new chemical entities on respiratory function in animal models is an essential component of preclinical drug safety evaluation. Methods currently available for measuring ventilatory parameters in conscious dogs generally utilize a plethysmograph chamber or a face mask equipped with a pneumotachograph attached to the snout of the animal. These methods require restraint and allow for only short, periodic measurements. Because of these limitations, respiratory inductive plethysmography (RIP) was evaluated as a possible new methodology that will allow for continuous monitoring of respiratory parameters in non-restrained dogs for extended periods of time. METHODS: Straps containing inductive coils were placed around the thorax and abdomen to measure thoracic and abdominal excursions. The straps were contained within a protective jacket that was placed on the dogs and the electrical signals from the inductive coils were transmitted by telemetry to a receiver. The data were acquired and analyzed using the Vivometrics(R) LifeShirt(R) PreClinical System. Because postural changes can alter tidal volume measurements using RIP, the jacket also contained an accelerometer that was used to record postural changes during ventilatory measurements. RESULTS: Measurement of ventilatory parameters in dogs following manual placement in different positions (e.g., standing, sitting, lateral recumbent) or during the different postures in non-restrained dogs demonstrated that changes in posture had only a minimal influence (

Comparative study on effectiveness of doxapram and pethidine for postanaesthetic shivering.

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. METHODS: Patients were randomly divided into three groups, ten in each. All received volume of 3 ml as Group I (Doxapram 1.5 mg/kg), Group II (Pethidine 0.35 mg/kg) and Group III (Normal Saline). All patients were observed for 30 minutes after reversal of muscle relaxant and occurrence of shivering within this period was observed, scored and treated. All treated patients were observed for 10 minutes after the test drug was given for control of shivering and any untoward effects. RESULTS: Pethidine was found more effective than Doxapram in treating postanaesthetic shivering as it was effective in 80% followed by Doxapram in 60% and Normal saline in 20%. Statistically the results between Normal saline and Pethidine was significant as P < 0.05. As statistical significance between Doxapram and Normal Saline was p = 0.16; and between Pethidine and Doxapram was p = 0.62, the difference is statistically not significant. CONCLUSIONS: Pethidine was found to be more effective compared to Doxapram in treating patients with postoperative shivering.

Difficult extubation in low birthweight infants.

Randomised trials have demonstrated that ventilation techniques which support every spontaneous breath are the most efficacious weaning modes. Nasal continuous positive airway pressure after extubation reduces the likelihood of incidents leading to the need for reintubation in very low birthweight infants; further work is needed to determine if there are advantages of particular delivery techniques. Both methylxanthines and dexamethasone facilitate weaning and extubation; the efficacy of low-dose dexamethasone merits further investigation. Assessments of the efficacy of respiratory efforts and hence the balance of respiratory drive, muscle performance and respiratory load appear to best predict weaning and extubation success. Essential to the success of weaning and extubation are dedicated staff, whether this will be assisted by computerised decision-making tools requires testing. The above approaches are not mutually exclusive and those indicated by this review as appropriately evidence based should be considered by practitioners for current use to reduce difficult/unsuccessful extubation.

Dynamic QT/RR relationship of cardiac conduction in premature infants treated with low-dose doxapram hydrochloride.

Doxapram hydrochloride, a respiratory stimulant, has several undesirable side effects during high-dose administration, including second-degree atrioventricular (AV) block and QT prolongation. In Japan, this drug is contraindicated for newborn infants. Recent studies, however, have demonstrated the efficacy and safety of doxapram therapy for apnea of prematurity (AOP) using lower doses than those previously tested. As a result, approximately 60% of Japanese neonatologists continue to use this drug. This study used surface ECG recordings to assess the cardiac safety of low-dose doxapram hydrochloride (0.2 mg/kg/h) in fifteen premature very-low-birth-weight infants with idiopathic AOP. Cardiac intervals and number of apnea episodes were compared before and after drug administration. Low-dose doxapram hydrochloride resulted in approximately 90% reduction in the frequency of apnea without side effects. None of the infants developed QT or PR prolongation, arrhythmia, or other conduction disorders. In addition, there was no change in the slope of QT/RR before versus after administration of doxapram hydrochloride. We conclude that low-dose administration of doxapram hydrochloride did not have any undesirable effects on myocardial depolarization and repolarization.