Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial).

BACKGROUND: Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age. METHODS: The DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18-24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle. DISCUSSION: Doxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020.

Pharmacologic interventions for the therapy of postanesthetic shivering in adults: a systematic review and network meta-analysis.

INTRODUCTION: Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare but can occur due to increased oxygen consumption. Previous systematic reviews are outdated and have summarized the evidence on the topic using only pairwise comparisons. The objective of this manuscript was a quantitative synthesis of evidence on pharmacological interventions to treat postanesthetic shivering. EVIDENCE ACQUSITION: Systematic review and frequentist network meta-analysis using the R package netmeta. Endpoints were the risk ratio (RR) of persistent shivering at one, five and 10 minutes after treatment with saline/placebo as the comparator. Data were retrieved from Medline, Embase, Central and Web of Science up to January 2022. Eligibility criteria were: randomized, controlled, and blinded trials comparing pharmacological interventions to treat shivering after general anesthesia. Studies on shivering during or after any type of regional anesthesia were excluded as well as sedated patients after cardiac surgery. EVIDENCE SYNTHESIS: Thirty-two trials were eligible for data synthesis, including 28 pharmacological interventions. The largest network included 1431 patients. The network geometry was two-centered with most comparisons linked to saline/placebo or pethidine. The best interventions were after one minute: doxapram 2 mg/kg, tramadol 2 mg/kg and nefopam 10 mg, after 5 minutes: tramadol 2 mg/kg, nefopam 10 mg and clonidine 150 µg and after 10 minutes: nefopam 10 mg, methylphenidate 20 mg and tramadol 1 mg/kg, all reaching statistical significance. Pethidine 25 mg and clonidine 75 µg also performed well and with statistical significance in all networks. CONCLUSIONS: Nefopam, tramadol, pethidine and clonidine are the most effective treatments to stop postanesthetic shivering. The efficacy of doxapram is uncertain since different doses showed contradictory effects and the evidence for methylphenidate is based on a single comparison in only one network. Furthermore, both lack data on side effects. Further studies are needed to clarify the efficacy of dexmedetomidine to treat postanesthetic shivering.

Effect of doxapram on the electrical activity of the diaphragm waveform pattern of preterm infants.

OBJECTIVE: This study aimed to evaluate the change in the waveform pattern of the electrical activity of the diaphragm (Edi) following the administration of doxapram in extremely preterm infants ventilated with neurally adjusted ventilatory assist (NAVA). STUDY DESIGN: We conducted this retrospective cohort study in our neonatal intensive care unit between November 2019 and September 2021. The study participants were extremely preterm infants under the gestational age of 28 weeks who were ventilated with NAVA and administered doxapram. We collected the data of the Edi waveform pattern and calculated the proportion. To analyze the change in the proportion of the Edi waveform pattern, we compared the proportion of the data for 1 h before and after doxapram administration. RESULTS: Ten extremely preterm infants were included. Almost all the patients' respiratory condition improved after doxapram administration. The ventilatory parameters-Edi peak, Edi minimum, peak inspiratory pressure, time in backup ventilation, and number of switches to backup ventilation-did not change significantly. However, the proportion of phasic pattern significantly increased (before: 46% vs. after: 72%; p < 0.05), whereas the central apnea pattern significantly decreased after doxapram administration (before: 31% vs. after: 8.3%; p < 0.05). The proportion of irregular low-voltage patterns tended to decrease, albeit with no significant changes. CONCLUSION: Our results indicated that the proportion of Edi waveform patterns changed following doxapram administration. Edi waveform pattern analysis could be a sensitive indicator of effect with other intervention for respiratory conditions.

Influence of doxapram and intermittent 10% carbon dioxide inspiration on cardiovascular and laryngeal functions in anesthetized dogs.

OBJECTIVE: To compare the effects of two doses of doxapram intravenous injection and carbon dioxide inhalation on the cardiovascular and laryngeal functions of anesthetized hounds. STUDY DESIGN: Experimental study. ANIMALS: Six healthy adult dogs. METHODS: In a Latin-square design, the mean arterial blood pressure (MABP) and heart rate (HR) were recorded continuously. The inspiratory normalized glottic gap areas (iNGGA) were measured before and after each stimulation with 0.55 mg/kg of doxapram (L-DOX), 2.2 mg/kg of doxapram (H-DOX), or 90 s of inhalation of 10% carbon dioxide in oxygen (I-CO2 ). The stimulations were tested in duplicate or triplicate. Video clips of the laryngeal movement were scored by board-certified surgeons masked to the treatment. RESULTS: The MABP increased with L-DOX and H-DOX up to 81% (both p < .001 compared to I-CO2 ), and persisted during the other stimulations (both p < .001). An intermittent tachycardic effect of up to 79% increase in HR was observed with doxapram. The HR following H-DOX was higher than L-DOX and I-CO2 (both p < .016). Neither hypertension nor tachycardia was observed with I-CO2 . The iNGGA increased with all treatments (p < .001). The iNGGA was greater with H-DOX than L-DOX and I-CO2 (both p < .007). All treatments received higher scores (all p < .001) with acceptable inter- and intra-observers Krippendorff's alphas. CONCLUSION: All treatments were effective respiratory stimulants in anesthetized dogs; however, doxapram caused hypertension and tachycardia. CLINICAL SIGNIFICANCE: Carbon dioxide inhalation might improve arytenoid motion without cardiovascular effects in dogs during clinical airway examinations.

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.

The effects of doxapram on time to tracheal extubation and early recovery in young morbidly obese patients scheduled for bariatric surgery: A randomised controlled trial.

BACKGROUND: Bariatric surgery is a well established treatment of the obese. Postoperative respiratory failure and airway obstruction after bariatric surgery can often be attributed to the residual depressant effects of anaesthetics, sedatives and opioids. Peri-operative management of morbidly obese patients is still a concern for operating room professionals. OBJECTIVE: The evaluation of the effects of doxapram on the outcomes of general anaesthesia following bariatric surgical procedures in the morbidly obese. DESIGN: A single-blind randomised controlled trial with two parallel arms. SETTING: A tertiary care teaching hospital, Tehran, Iran, from 2017 to 2018. PARTICIPANTS: In total, 100 patients (69 women) with at least class two obesity were included in two groups of equal sizes and underwent bariatric surgery. MAIN OUTCOME MEASURES: The primary outcome was the time from the administration of doxapram to tracheal extubation. Secondary outcomes included vital signs and variables including peak expiratory flow rate, time to return to spontaneous breathing, time to eye-opening and hand-squeezing on the commands, and time to recovery. INTERVENTIONS: Both groups underwent general anaesthesia. The intervention group received a single dose of doxapram 1 mg kg ideal body weight, immediately after reversal of neuromuscular blockade and after discontinuation of all anaesthetics. RESULTS: Doxapram decreased time to extubation, time to eye-opening and hand-squeezing, shortened recovery time and lowered end-tidal CO2 significantly (all P < 0.001). Moreover, it increased peak expiratory flow rate, oxygen saturation, temperature, heart rate and blood pressure (all P < 0.001). The two groups were similar in the bispectral index and mean arterial pressure (both P > 0.05). None of our participants had complications attributable to doxapram. CONCLUSION: The postoperative use of doxapram improves peak expiratory flow rate, and decreases respiratory complications of anaesthesia during recovery in the morbidly obese undergoing bariatric surgery. Doxapram is well tolerated in young ASA physical status classes 1 to 2 morbidly obese patients; however, the anaesthesiologist should cautiously evaluate the vital signs for at least half an hour following the administration of doxapram. REGISTRATION: Iranian Registry of Clinical Trials (IRCT) http://www.irct.ir/ number IRCT2017060712203N9.

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).

Comparison of methohexital and propofol as induction agents for evaluation of laryngeal function in healthy dogs.

OBJECTIVE: To determine the influence of propofol or methohexital, with and without doxapram, on the examination of laryngeal function in dogs. STUDY DESIGN: Experimental study. ANIMALS: Forty healthy dogs randomly assigned to 4 groups: propofol with saline (n = 10), propofol with doxapram (n = 10), methohexital with saline (n = 10), or methohexital with doxapram (n = 10). METHODS: Propofol and methohexital were administered to effect. Investigators examined laryngeal function (initial) simultaneously with video laryngoscopy. Doxapram or saline was administered, and laryngeal function was reevaluated (second). Laryngeal motion, quality of laryngeal exposure, and the degree of swallowing, laryngospasm, and jaw tone were scored at each evaluation. Adverse events were recorded. Initial and second videos were evaluated by a masked observer, and still images obtained from both evaluations were evaluated for change in rima glottidis size by 2 masked observers. RESULTS: Administration of doxapram and saline was delayed with propofol (P = .001). Laryngeal function did not differ between dogs receiving propofol or methohexital, irrespective of doxapram administration. Doxapram improved breathing scores in both groups (P < .001). Jaw tone increased with propofol during the second evaluation (P = .049). Swallowing was more prevalent at initial examination (P = .020). Methohexital resulted in an increased heart rate (P < .001) compared with propofol. Twenty-five percent of dogs receiving methohexital developed seizure-like activity (n = 5/20). CONCLUSION: Evaluation of laryngeal function did not differ between healthy dogs anesthetized with propofol or methohexital. Methohexital provided shorter examination times with less jaw tone but was associated with adverse events. CLINICAL SIGNIFICANCE: This study provides evidence to recommend propofol over methohexital as an induction agent for laryngeal function examination.

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.

Combating Multidrug-Resistant Pathogens with Host-Directed Nonantibiotic Therapeutics.

Earlier, we reported that three Food and Drug Administration-approved drugs, trifluoperazine (TFP; an antipsychotic), amoxapine (AXPN; an antidepressant), and doxapram (DXP; a breathing stimulant), identified from an in vitro murine macrophage cytotoxicity screen, provided mice with 40 to 60% protection against pneumonic plague when administered at the time of infection for 1 to 3 days. In the present study, the therapeutic potential of these drugs against pneumonic plague in mice was further evaluated when they were administered at up to 48 h postinfection. While the efficacy of TFP was somewhat diminished as treatment was delayed to 24 h, the protection of mice with AXPN and DXP increased as treatment was progressively delayed to 24 h. At 48 h postinfection, these drugs provided the animals with significant protection (up to 100%) against challenge with the agent of pneumonic or bubonic plague when they were administered in combination with levofloxacin. Likewise, when they were used in combination with vancomycin, all three drugs provided mice with 80 to 100% protection from fatal oral Clostridium difficile infection when they were administered at 24 h postinfection. Furthermore, AXPN provided 40 to 60% protection against respiratory infection with Klebsiella pneumoniae when it was administered at the time of infection or at 24 h postinfection. Using the same in vitro cytotoxicity assay, we identified an additional 76/780 nonantibiotic drugs effective against K. pneumoniae For Acinetobacter baumannii, 121 nonantibiotic drugs were identified to inhibit bacterium-induced cytotoxicity in murine macrophages. Of these 121 drugs, 13 inhibited the macrophage cytotoxicity induced by two additional multiple-antibiotic-resistant strains. Six of these drugs decreased the intracellular survival of all three A. baumannii strains in macrophages. These results provided further evidence of the broad applicability and utilization of drug repurposing screening to identify new therapeutics to combat multidrug-resistant pathogens of public health concern.

Effects of Neuroactive Drugs in the Discharge Patterns of Microsternarchus (Hypopomidae: Gymnotiformes) Electric Organ.

Considering the conserved nature of synaptic physiology among vertebrates, we tested the effects of three psychotropics (diazepam, doxapram, and nicotine) on Microsternarchus cf. bilineatus, measuring 10 parameters associated to the electric organ discharges rhythm and waveform before and after the administration of each drug and a control group. There were statistically significant differences (p < 0.005) among all the experimental groups, F (70, 22619.25) = 77.7, between the two experimental phases within their respective drug treatment, F (80, 24604.51) = 16.0, and among the six experimental hours within their respective phases and groups, F (320, 37124.15) = 4.1. We observed a common general trend of reduction in the electric organ's (EO) firing rate, regardless of the expected stimulant or depressor effect of the drugs on the central nervous system (CNS). The intensity of the response changed with the treatment. The observed changes in the fishes' behavior may be a result of the drugs' direct action on the CNS or a combination of this with systemic effects of each substance tested, also in the EO.

New Role for FDA-Approved Drugs in Combating Antibiotic-Resistant Bacteria.

Antibiotic resistance in medically relevant bacterial pathogens, coupled with a paucity of novel antimicrobial discoveries, represents a pressing global crisis. Traditional drug discovery is an inefficient and costly process; however, systematic screening of Food and Drug Administration (FDA)-approved therapeutics for other indications in humans offers a rapid alternative approach. In this study, we screened a library of 780 FDA-approved drugs to identify molecules that rendered RAW 264.7 murine macrophages resistant to cytotoxicity induced by the highly virulent Yersinia pestis CO92 strain. Of these compounds, we identified 94 not classified as antibiotics as being effective at preventing Y. pestis-induced cytotoxicity. A total of 17 prioritized drugs, based on efficacy in in vitro screens, were chosen for further evaluation in a murine model of pneumonic plague to delineate if in vitro efficacy could be translated in vivo Three drugs, doxapram (DXP), amoxapine (AXPN), and trifluoperazine (TFP), increased animal survivability despite not exhibiting any direct bacteriostatic or bactericidal effect on Y. pestis and having no modulating effect on crucial Y. pestis virulence factors. These findings suggested that DXP, AXPN, and TFP may modulate host cell pathways necessary for disease pathogenesis. Finally, to further assess the broad applicability of drugs identified from in vitro screens, the therapeutic potential of TFP, the most efficacious drug in vivo, was evaluated in murine models of Salmonella enterica serovar Typhimurium and Clostridium difficile infections. In both models, TFP treatment resulted in increased survivability of infected animals. Taken together, these results demonstrate the broad applicability and potential use of nonantibiotic FDA-approved drugs to combat respiratory and gastrointestinal bacterial pathogens.

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.

The effects of doxapram on medullary respiratory neurones in brainstem-spinal cord preparations from newborn rats.

Doxapram is the only dedicated respiratory stimulant used to aid recovery of breathing after major surgery. Doxapram acts on peripheral chemoreceptors and although the central action of doxapram has been suggested, its detailed neuronal mechanism is unknown. We assessed doxapram-induced changes in spontaneous cervical nerve (C4) inspiratory activity and the firing of action potentials in pre-inspiratory and inspiratory neurones in the medulla. Experiments were performed in neonatal rat brainstem-spinal cord preparations, which can produce respiratory rhythm for several hours under in vitro conditions. Doxapram application (for 15 min) increased the frequency and amplitude of C4 activity dose-dependently. Doxapram induced changes in the electrophysiological properties of pre-inspiratory and inspiratory neurones. Our results suggest that respiratory activity enhancement was likely to be induced via effects on the potassium channels of pre-inspiratory and inspiratory neurones and indicate the central actions of doxapram.

Effects of doxapram, prethcamide and lobeline on spirometric, blood gas and acid-base variables in healthy new-born calves.

A number of drugs have been used to treat asphyxia in new-born calves and the aim of the current study was to investigate the effect of commonly-used stimulant drugs on ventilation, arterial blood gas and acid base variables. A group (n=18) of new-born (3-15 h old) calves were treated in a randomised sequence with doxapram (40 mg, IV), lobeline (5mg, IV) or prethcamide (5 mL, consisting of 375 mg crotethamide and 375 mg cropropamide, buccally). Blood and spirometric measurements, using an ultrasonic spirometer, were collected prior to and 1, 5, 15, 30, 60, 90 min after administration of each drug. Doxapram caused a significant increase in the respiratory rate, peak inspiratory and expiratory flow and minute volume (V(min)) during the 90-min post-treatment study period, although maximum values occurred 1 min after treatment. The V(min) increased from 13.8 ± 5.0 L to 28.5 ± 12.3 L. Prethcamide, but not lobeline, also caused significant increases in inspiratory and expiratory volumes. The effects of doxapram on ventilation were accompanied by an increase in arterial partial pressure of oxygen (P(a)O(2)) (77.7 ± 18.8 mm Hg to 93.2 ± 23.7 mm Hg), a decrease in arterial partial pressure of carbon dioxide (P(a)CO(2)) (42.6 ± 4.9 mm Hg to 33.1 ± 6.6mm Hg), a significant increase in pH and a decrease in bicarbonate concentration and base excess 1 min after treatment. Prethcamide caused a gradual increase in P(a)O(2) and decrease in P(a)CO(2) over 90 min, whereas lobeline had no measurable effect on the investigated variables. Of the three treatments, only doxapram had a distinct stimulatory effect on respiration in healthy neonatal calves and may therefore be useful in the treatment of calf asphyxia.

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.

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.