OBJECTIVETo investigate the effects of doxapram on the respiratory rhythmical discharge activity (RRDA) in the brainstem slices of neonatal rats.

METHODSThirty neonatal SD rats (of either sex, 0-3 days old) were randomly divided into 6 equal groups (groups I-VI), and the brainstem slices which contained the medial region of the nucleus retrofacialis (mNRF) were prepared. All the slices were perfused with modified Kreb's solution (MKS), and in group I (control group), the slices were perfused with MKS only; in groups II to IV, the slices were perfused with doxapram in MKS continuously at the concentrations of 2, 5, and 10 micromol/L, respectively; in groups V and VI, the slices were perfused with 20 micromol/L propofol and 20 micromol/L propofol plus 5 micromol/L doxapram, respectively. The RRDA in the hypoglossal nerve was recorded by suction electrode. The discharge time course of the inspiratory (TI), expiratory (TE), respiratory cycle (RC) and integral amplitude of the inspiratory discharge (IA) were recorded at 1, 3, 5, 10, 15, and 30 min after the application of the drugs.

RESULTSThe hypoglossal nerve in groups I, II and VI showed no significant changes of RRDA in the entire course of the experiment (P>0.05). In groups III and IV, the TI, IA increased and TE decreased significantly 5 min after doxapram application (P<0.05), and the RC was shortened only at 10 min. In group V, the TI and IA decreased and the RC and TE increased significantly after the drug application (P<0.05).

CONCLUSIONDoxapram (>5 micromol/L ) can directly stimulate the RRDA and prevent propofol-induced inhibitory effects in the brainstem slice of neonatal rats, and the effects are mediated by its actions upon the inspiratory neurons in the mNRF.

Animals ; Animals, Newborn ; Doxapram ; pharmacology ; Electrophysiological Phenomena ; drug effects ; Female ; In Vitro Techniques ; Male ; Medulla Oblongata ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Respiration ; drug effects ; Respiratory System Agents ; pharmacology

Doxapram is a peripheral and central respiratory stimulant, producing an increase in tidal volume and a slight increase in respiratory rate. It can temporarily overcome drug-induced respiratory and central nervous system depression, including that seen immediately postoperatively. However, it can also cause side effects, including laryngospasm and vomiting postoperatively. Doxapram-induced laryngospasm causes the increased respiratory efforts to induce more negative pleural pressure, thus causing a negative-pressure pulmonary edema.Therefore, doxapram should not be used if signs of upper airway obstruction are present.
Airway Obstruction ; Central Nervous System ; Depression ; Doxapram ; Laryngismus ; Pulmonary Edema ; Respiratory Rate ; Tidal Volume ; Vomiting

BACKGROUND: Doxapram hydrochloride is a respiratory stimulant that produces arousal effects in patients under anesthesia. We investigated the effects of doxapram on the recovery time and BIS index of patients administered desflurane inhalational anesthesia. METHODS: 40 patients who underwent general anesthesia using desflurane that had an ASA physical status of I or II received either 1 mg/kg of doxapram hydrochloride (doxapram group, n = 20) or normal saline (control group, n = 20) IV at end of surgery. Anesthetic recovery after the injection of doxapram was then determined based on the time to eye opening in response to verbal command, hand squeezing on command, time to extubation, and Aldrete recovery score. BIS index, systolic blood pressure, tidal volume and heart rate were recorded every minute for up to thirteen minutes. RESULTS: The doxapram group showed significantly shorter times to emergence based on eye opening in response verbal command (sec) (409 +/- 114 vs 320 +/- 116), hand squeezing on command (sec) (458 +/- 119 vs 351 +/- 114) and extubation (sec) (491 +/- 103 vs 418 +/- 79) compared to control group. The BIS score was not significantly different between the two groups. CONCLUSIONS: The Bis index was not significant higher in the doxapram group, with the exception of the measurement recorded at 2 minutes, however the recovery time from desflurane inhalational anesthesia was faster in the doxapram group than the control group.
Anesthesia ; Anesthesia, General ; Arousal ; Blood Pressure ; Doxapram ; Eye ; Hand ; Heart Rate ; Humans ; Isoflurane ; Tidal Volume

BACKGROUND: The aim of this study was to investigate the effect of doxapram on recovery following propofol-remifentanil anesthesia. METHODS: Forty patients scheduled for gastrectomy were randomly allocated to receive either doxapram 1 mg/kg or normal saline at the end of surgery under propofol-remifentanil anesthesia. Clinical recovery from anesthesia was assessed by times to spontaneous breathing, eye opening on verbal command, extubation, and discharge from the postanesthetic care unit (PACU). Bispectral index (BIS) values, blood pressure, and heart rate were recorded every 2 min for 16 min after the administration of doxapram or saline. The incidences of side effects were checked in the recovery room. RESULTS: Spontaneous breathing was recovered after 6.2 +/- 1.1 minutes in the Doxapram group versus 9.2 +/- 1.8 minutes in the normal saline group (P < 0.001). Times to eye and extubation were also shorter in the Doxapram patients than in the normal saline patients (6.9 +/- 1.0 and 8.1 +/- 1.7 min versus 10.4 +/- 2.0 and 12.0 +/- 2.6 min, respectively) (P < 0.001). However, the times to PACU discharge were not different between the two groups (46.9 +/- 4.9 min versus 47.0 +/- 6.0 min, respectively). The patients in the Doxapram group showed higher mean BIS values compared with the normal saline group during emergence, but there were no differences in arterial blood pressure, heart rate and incidences of side effects between the two groups. CONCLUSIONS: Doxapram 1 mg/kg hastens early recovery from TIVA with propofol and remifentanil, and this emergence effect correlates with higher BIS values. Doxapram, however, does not affect the discharge time from the PACU and incidences of side effects.
Anesthesia ; Anesthesia, Intravenous ; Arterial Pressure ; Blood Pressure ; Doxapram ; Eye ; Gastrectomy ; Heart Rate ; Humans ; Incidence ; Piperidines ; Propofol ; Recovery Room ; Respiration

BACKGROUND: The aim of this study was to investigate the effect of doxapram on recovery following propofol-remifentanil anesthesia. METHODS: Forty patients scheduled for gastrectomy were randomly allocated to receive either doxapram 1 mg/kg or normal saline at the end of surgery under propofol-remifentanil anesthesia. Clinical recovery from anesthesia was assessed by times to spontaneous breathing, eye opening on verbal command, extubation, and discharge from the postanesthetic care unit (PACU). Bispectral index (BIS) values, blood pressure, and heart rate were recorded every 2 min for 16 min after the administration of doxapram or saline. The incidences of side effects were checked in the recovery room. RESULTS: Spontaneous breathing was recovered after 6.2 +/- 1.1 minutes in the Doxapram group versus 9.2 +/- 1.8 minutes in the normal saline group (P < 0.001). Times to eye and extubation were also shorter in the Doxapram patients than in the normal saline patients (6.9 +/- 1.0 and 8.1 +/- 1.7 min versus 10.4 +/- 2.0 and 12.0 +/- 2.6 min, respectively) (P < 0.001). However, the times to PACU discharge were not different between the two groups (46.9 +/- 4.9 min versus 47.0 +/- 6.0 min, respectively). The patients in the Doxapram group showed higher mean BIS values compared with the normal saline group during emergence, but there were no differences in arterial blood pressure, heart rate and incidences of side effects between the two groups. CONCLUSIONS: Doxapram 1 mg/kg hastens early recovery from TIVA with propofol and remifentanil, and this emergence effect correlates with higher BIS values. Doxapram, however, does not affect the discharge time from the PACU and incidences of side effects.
Anesthesia ; Anesthesia, Intravenous ; Arterial Pressure ; Blood Pressure ; Doxapram ; Eye ; Gastrectomy ; Heart Rate ; Humans ; Incidence ; Piperidines ; Propofol ; Recovery Room ; Respiration

BACKGROUND: Intravenous anesthetics causes depression of ventilatory response to hypercapnea. Doxapram stimulates ventilation via peripheral and central chemoreceptors. This study was aimed to evaluate the effect of doxapram on ventilation during total intravenous anesthesia (TIVA). METHODS: 60 patients undergoing operation under spontaneous ventilation via laryngeal mask airwaywere randomly divided into 3 groups: Control group received 5% dextrous infusion, D-2 group received doxapram injection of 1 mg/kg followed by continuous infusion of 2 mg/kg/hr, and D-4 group received doxapram injection of 2 mg/kg followed by continuous infusion of 4 mg/kg/hr. Anesthesia was induced and maintained with propofol and remifentanil. Respiratory rate, tidal volume (VT) and arterial carbon dioxide tension (PaCO2) were measured before and 15 min after induction of anesthesia, 0(15 min after start of operation), 1, 2, 3, 5, 15, 30, 45, and 60 min after start of doxapram infusion during TIVA. RESULTS: VT was significantly increased 1 min after start of doxapram infusion and returned to the value of pre-doxapram infusion immediately. In D-4 group, VT was significantly (P < 0.05) increased again 5 min after doxapram infusion compared with the value of pre-doxapram infusion and control group. PaCO2 was decreased 1 min after start of doxapram infusion and then increased again 2 min after doxapram infusion. In D-4 group, the degree of increase of PaCO2 was significantly (P < 0.05) less than those of D-2 group. CONCLUSIONS: Doxapram injection of 2 mg/kg followed by continuous infusion of 4 mg/kg/hr improved the depression of ventilatory response during TIVA.
Anesthesia ; Anesthesia, Intravenous* ; Anesthetics, Intravenous ; Carbon Dioxide ; Depression ; Doxapram* ; Humans ; Laryngeal Masks* ; Propofol ; Respiratory Insufficiency ; Respiratory Rate ; Tidal Volume ; Ventilation*

OBJECTIVETo observe the impacts of doxapram on anesthetic efficacy and respiratory and circulatory functions during anesthesia with remifentanil given by target-controlled infusion (TCI) combined with propofol in painless artificial abortion.

METHODSA total of 120 ASA I women requiring voluntarily painless artificial abortion were randomized into two equal groups. One group was given remifentanil by TCI at 2 ng/ml and propofol 1mg/kg (group I), and the other given remifentanil by TCI, propofol, and doxapram 0.6 mg/kg (group II). The anesthetic efficacy and respiratory and circulatory suppression during anesthesia were observed.

RESULTSBoth of the two groups showed satisfactory anesthetic efficacy with comparable the BIS values (P>0.05). No significant difference was noted in the induction time and awaking time between the two groups (P>0.05), but group I had more serious respiratory and circulatory depression than group II (P<0.05).

CONCLUSIONDoxapram may attenuate respiratory and circulatory depression during anesthesia with remifentanil given by TCI combined with propofol in painless artificial abortion, and provide comparable anesthetic efficacy.

Abortion, Induced ; Adolescent ; Adult ; Anesthetics, Combined ; Doxapram ; administration & dosage ; Female ; Humans ; Infusions, Intravenous ; Middle Aged ; Piperidines ; administration & dosage ; Propofol ; administration & dosage ; Treatment Outcome

OBJECTIVE: To develop a specific, sensitive, reproducible SPE-HPLC method for the determination of 37 drugs in whole blood. METHODS: With the doxapram as internal standard, Oasis column was used to extract drugs from whole blood. Two kinds of mobile phases were used in this study. Separations were achieved by a LiChrospher 100 RP-C18 (250 mm x 4.0 mm x 5 microm) column kept at 50 degrees C, the DAD detector was set at 230 nm and 250 nm. RESULTS: The limit of detection were 1-30 ng/mL. The method showed excellent linearity and the linear correlation coefficient was > or =0.997 98. The relative standard deviation for between-day and within-day assay were <10%. CONCLUSION The method is effective, simple, reliable and has been used in real cases.
Chromatography, High Pressure Liquid/methods* ; Doxapram/isolation & purification* ; Doxepin/isolation & purification* ; Estazolam/isolation & purification* ; Forensic Medicine ; Humans ; Morphine/isolation & purification* ; Papaverine/isolation & purification* ; Pharmaceutical Preparations/isolation & purification* ; Prazosin/isolation & purification* ; Procaine/isolation & purification* ; Reproducibility of Results ; Sensitivity and Specificity ; Solid Phase Extraction/methods* ; Solvents/chemistry*

OBJECTIVE: To develop a specific CZE method for the determination of methamphetamine in whole blood after solid phase extraction. METHODS: With the doxapram as internal standard, Oasis column was used to extract drugs from whole blood and the sample was analysized by CZE. RESULTS: The method showed excellent linearity and the linear correlation coefficient was 0.994. The relative standard deviation for between-day and within-day were 5.31% and 2.22%, respectively. CONCLUSION The method is effective, simple, reliable and has been used in the determination of methamphetamine in whole blood.
Doxapram/chemistry* ; Electrophoresis, Capillary/methods* ; Forensic Medicine ; Gas Chromatography-Mass Spectrometry ; Humans ; Methamphetamine/poisoning* ; Reproducibility of Results ; Sensitivity and Specificity ; Solid Phase Extraction ; Solvents/chemistry*

BACKGROUND: Inhalation anesthetics are known to depress ventilatory response to hypercapnea. Doxapram hydrochloride is an analeptic drug, which acts as a respiratory stimulant via peripheral and central chemoreceptors. Although the postoperarive infusion of doxapram hydrochloride is known to attenuate the impairment of respiratory function, no report is available on respiratory response to this drug when applied during anesthesia. Therefore, the present study aimed to evaluate the effect of doxapram hydrochloride on respiratory function during anesthesia. METHODS: Sixty adult patients undergoing operation under spontaneous ventilation via laryngeal mask airway (LMA) were randomly categorized into 3 groups: A control group, which received 5% dextrous infusion, and two groups in which patients were infused with doxapram hydrochloride (0.5 or 2 mg/kg/hr) starting 15 min after commencement operation. Anesthesia was maintained with 1 MAC sevoflurane - 4 L N2O - 2 L O2 under spontaneous ventilation via LMA. Tidal volume (VT), respiratory rate (RR), and arterial carbon dioxide tension (PaCO2) were measured just before and 15 min after the induction of anesthesia, 15 min after the start of operation and 15, 30, 45, and 60 min after the start of doxapram hydrochloride infusion. RESULTS: Measured values of RR and PaCO2 were significantly elevated during anesthesia venous those measured just before the induction of anesthesia in all groups. VT was significantly reduced during anesthesia venous just before the induction of anesthesia in all groups. All percent changes of VT, RR and PaCO2 were similar all any measurement times, and showed no significant changes after the infusion of doxapram hydrochloride in all groups. CONCLUSIONS: Intraoperative doxapram hydrochloride treatment did not produce any significant respiratory response improvement during 1 MAC sevoflurane anesthesia.
Adult ; Anesthesia ; Anesthesia, General* ; Anesthetics, Inhalation ; Carbon Dioxide ; Doxapram* ; Humans ; Laryngeal Masks* ; Respiratory Insufficiency ; Respiratory Rate ; Tidal Volume ; Ventilation*