Propofol or midazolam for short-term alterations in sedation

It is often necessary to adjust a patient’s sedation level while they are in the intensive care unit. The purpose of this study was to compare propofol with midazolam for controlling short-term alterations in sedation. Twenty-three patients undergoing an interactive procedure, physiotherapy, during mechanical ventilation of the lungs were studied. The patients were randomly assigned to receive infusions of propofol or midazolam for sedation. Sedation was assessed using the method of Ramsay, where 3 is drowsy responding only to commands; and 5 is asleep with a slow response to light glabellar tap. Prior to physiotherapy sedation was deepened from 3 to 5 by increasing the sedative infusion rate, and level 5 was maintained during physiotherapy by adjusting the infusion rate whenever necessary. After physiotherapy, the sedative dose was reduced until level 3 was again achieved. During physiotherapy, sedation level 5 was achieved for 53.9% of the time with propofol but for only 25.7% with midazolam (P < 0.01). After physiotherapy, those patients sedated with propofol re-awakened to level 3 faster (8.3 ± 2.3 min, mean ±SE) than those receiving midazolam (92.8 ± 35.0 min, P < 0.05). After physiotherapy, a further 1.8 ± 0.5 dose adjustments were required to the midazolam infusion while only 0.4 ± 0.2 adjustments were required to the propofol infusion (P < 0.05). During physiotherapy 3.0 ± 0.5 dose adjustments to the propofol dose were required compared with 3.6 ± 0.5 adjustments to the midazolam dose (NS). It is concluded that, during a standardized stimulus, physiotherapy, propofol infusion allowed a desired sedation score to be maintained for more of the time than did infusion of midazolam. Subsequently, when the infusion rates were reduced, less time was taken to re-awaken to baseline levels after physiotherapy, with fewer adjustments to the infusion rate, in those patients receiving propofol than midazolam.     

Comparison of midazolam sedation with or without fentanyl in cataract surgery

We compared the effect of midazolam sedation with or without fentanyl on the hemodynamic parameters, sedation, and pain and satisfaction profile in cataract surgery. Two hundred and ten patients were randomly allocated to receive either midazolam 1 mg i.v. (Group M, n = 101) alone or with fentanyl 25 microg (Group MF, n = 100) before retrobulbar injection. Hemodynamic parameters, observer's assessment of alertness/sedation (OAA/S) scores, pain during block and surgery, satisfaction of patient and surgeons were assessed. Heart rate and diastolic arterial pressure decreased after retrobulbar injection in comparison to baseline whereas systolic arterial pressure values increased in both groups. The majority of patients in both groups experienced mild pain during retrobulbar injection but no pain during surgery. There was a significant decrease in OAA/S scores in both groups (p = 0.001) and this decline was more significant in Group MF (p = 0.038). We suggest that midazolam alone may produce optimal block conditions for the patient and it is satisfactory during the procedure while the addition of fentanyl has not improved the effect on the examined parameters.     

Propofol or midazolam for sedation and early extubation following cardiac surgery

Purpose

The purpose of this randomized, double-blind study was to evaluate the efficacy of midazolam and propofol for postoperative sedation and early extubation following cardiac surgery.

Methods

ASA physical status II-III patients scheduled to undergo elective first-time cardiac surgery with an ejection fraction > 45% were eligible. All patients received a standardized sufentanil/isoflurane anaesthesa. Dunng cardiopulmonary bypass 100 μg · kg^?1· mm^?1 propofol was substituted for isoflurane. Upon amval in the Intensive Care Unit (ICU). patients were randomized to either 10 μg · kg · min^?1 propofol (n = 21) or 0.25 μg · kg · mm^?1 midazolam (n = 20). Infusion rates were adjusted to maintain sedation within a predetermined range (Ramsay 2–4). The infuson was terminated after four hours. Patients were weaned from mechanical ventilation and their tracheas extubated when haemodynamic stability, haemostasis, normothermia and mental orientation were confirmed. Haemodynamic measurements, artenal blood gas tensions and pulmonary function tests were recorded at specified times.

Results

There were no differences between the two groups for the time spent at each level of sedation, number of infusion rate adjustments, amount of analgesic and vasoactive drugs, times to awakening and extubation. The costs of propofol were higher than those of midazolam. There were no differences in haemodynamic values, artenal blood gas tensions and pulmonary function.

Conclusion

We conclude that midazolam and propofol are safe and effective sedative agents permitting early extubation in this selected cardiac patient population but propofol costs were higher.     

Frequent hypoxemia and apnea after sedation with midazolam and fentanyl

More than 80 deaths have occurred after the use of midazolam (Versed), often in combination with opioids, to sedate patients undergoing various medical and surgical procedures. We investigated the respiratory effects of midazolam (0.05 mg.kg-1) and fentanyl (2.0 micrograms.kg-1) in volunteers. The incidence of hypoxemia (oxyhemoglobin saturation less than 90%) and apnea (no spontaneous respiratory effort for 15 s) and the ventilatory response to carbon dioxide were evaluated. Midazolam alone produced no significant respiratory effects. Fentanyl alone produced hypoxemia in half of the subjects and significant depression of the ventilatory response to CO2, but did not produce apnea. Midazolam and fentanyl in combination significantly increased the incidence of hypoxemia (11 of 12 subjects) and apnea (6 of 12 subjects), but did not depress the ventilatory response to CO2 more than did fentanyl alone. Adverse reactions linked to midazolam and reported to the Department of Health and Human Services highlight apnea- and hypoxia-related problems as among the most frequent adverse reactions. Seventy-eight per cent of the deaths associated with midazolam were respiratory in nature, and in 57% an opioid had also been administered. All but three of the deaths associated with the use of midazolam occurred in patients unattended by anesthesia personnel. We conclude that combining midazolam with fentanyl or other opioids produces a potent drug interaction that places patients at a high risk for hypoxemia and apnea. Adequate precautions, including monitoring of patient oxygenation with pulse oximetry, the administration of supplemental oxygen, and the availability of persons skilled in airway management are recommended when benzodiazepines are administered in combination with opioids.     

Procedural sedation for insertion of central venous catheters in children: comparison of midazolam/fentanyl with midazolam/ketamine

Background: There is a lack of studies evaluating procedural sedation for insertion of central venous catheters (CVC) in pediatric patients in emergency departments or pediatric intensive care units (PICU). This study was designed to evaluate whether there is a difference in the total sedation time for CVC insertion in nonintubated children receiving two sedation regimens. Methods: Patients were prospectively randomized to receive either midazolam/fentanyl (M/F) or midazolam/ketamine (M/K) i.v. The Children's Hospital of Wiscosin Sedation Scale was used to score the sedation level. Results: Fifty seven patients were studied (28 M/F and 29 M/K). Group M/F received midazolam (0.24 ± 0.11 mg·kg⁻¹) and fentanyl (1.68 ± 0.83 μg·kg⁻¹) and group M/K received midazolam (0.26 ± 0.09 mg·kg⁻¹) and ketamine (1.40 ± 0.72 mg·kg⁻¹). The groups were similar in age, weight, risk classification time and sedation level. Median total sedation times for M/F and M/K were 97 vs 105 min, respectively (P = 0.67). Minor complications occurred in 3.5% (M/F) vs 20.7% (M/K) (P = 0.03). M/F promoted a greater reduction in respiratory rate (P = 0.005). Conclusions: In this study of nonventilated children in PICU undergoing central line placement, M/F and M/K provided a clinically comparable total sedation time. However, the M/K sedation regimen was associated with a higher rate of minor complications. A longer period of study is required to assess the efficacy and safety of these sedative agents for PICU procedures in nonintubated children.     

咪唑安定或丙泊酚伍用芬太尼对镇静深度和呼吸、循环的影响

目的　观察咪唑安定或丙泊酚伍用芬太尼对镇静和呼吸、循环的影响,探讨脑电双频 指数(BIS)与呼吸、循环参数的关系。方法　选择行四肢或下腹部手术患者40例,随机均分为四组: 丙泊酚组(P组)、丙泊酚加芬太尼组(PF组)、咪唑安定组(M组)和咪唑安定加芬太尼组(MF组)。 静注芬太尼0.05mg(1ml)或生理盐水1ml(观察者不知);丙泊酚负荷量1mg/kg,维持量0.05mg ·kg 1·min 1;咪唑安定负荷量0.1mg/kg,维持量0.01mg·kg 1·min 1。观察并每隔2分钟记录 患者呼吸指标(PETCO2、PaO2、PaCO2、SaO2等)及循环指标,并与BIS、95%边缘频率(95%SEF)和警 觉/镇静观察评分(OAA/S)进行相关分析。结果　观察期间各组无因循环指标达到“黄牌”而停药, 均因呼吸指标达到“黄牌”而停止给药。BIS与用药剂量呈负相关,与OAA/S和95%SEF呈正相关, BIS与PaCO2、PETCO2和RR呈负相关,与VT、VE、SpO2、SaO2呈正相关,PF组HR比P组慢(P< 0.01)。MF组的PETCO2、RR及HR与M组有明显变化(P<0.01)。结论　本研究条件下最合适 的镇静水平维持OAA/S评分2～3分、BIS72～80为宜,此时呼吸、血液动力学稳定,对手术刺激无 反应且能产生遗忘,同时对呼吸、循环抑制较轻。     

Withdrawal syndrome in a critically ill child after sedation with midazolam and fentanyl

A 7-year-old girl suffered from withdrawal syndrome with systemic convulsion after sedation with midazolam and fentanyl. She had a history of severe accidental alkaline esophagitis, and under went polysurgeries. This time, she was scheduled to receive reconstruction of the esophagus with small intestine in order to resolve esophageal stenosis. Operation and anesthesia lasted for 14 hours, and 17 hours, respectively. In the postoperative period, she was under heavy sedation with midazolam and fentanyl in order to keep neck position immobile. Her sedation persisted for 14 postoperative days, and the total doses of midazolam and fentanyl were more than 100 mg x kg(-1), and 6.4 mg x kg(-1), respectively. Thereafter, her sedation was tapered and discontinued within about 24 hours. After 12 hours, she suddenly developed systemic convulsion with loss of consciousness. There was no evidence of obvious organic central nervous system abnormality. We suspected withdrawal syndrome, and gradual decrease of midazolam and fentanyl prevented her from going into withdrawal syndrome. We have to pay attention to withdrawal syndrome when heavy and long sedation with midazolam and fentanyl was employed and the drugs were then tapered and discontinued.     

Propofol anaesthesia versus paracervical blockade with alfentanil and midazolam sedation for outpatient abortion

Propofol anaesthesia was compared with paracervical blockade in a prospective, randomized study of 59 abortion patients. All the patients received alfentanil 0.01 mg/kg i.v. at the start of anaesthesia and were randomized into two groups. Group R (regional, 31 patients): midazolam 0.1 mg/kg i.v. and paracervical blockade with 2 x 10 ml of mepivacaine 20 mg/ml + adrenaline 0.005 mg/ml. Group G (general, 28 patients): propofol 2.0 mg/kg i.v. induction and 75% nitrous oxide in oxygen spontaneous respiration. In 10 patients from the R-group venous blood samples were taken regularly for 30 min for serum concentration measurements (gas chromatography) of mepivacaine. Pain during induction of anaesthesia was remembered by 17% in Group G and 4% in Group R, whereas 8% in Group R remembered pain during the procedure compared with none in Group G. Of the patients in Group G, 25% had apnoea compared with none in Group R. In Group R the patients slept for 2.5 +/- 3.8 min (mean +/- s.d.) after induction compared with 12 +/- 4.0 min in Group G. Except for a better p-deletion score 30 min after the procedure in Group G, there was no difference in recovery function between the groups. Of the patients in Group G, 67% experienced postoperative pain compared with 23% in Group R. Maximum serum mepivacaine concentration (Group R) was reached at 15-30 min, range 1.5-5 micrograms/ml.     

Bispectral index as a predictor of sedation depth during isoflurane or midazolam sedation in ICU patients

Bispectral index (BIS) is used for monitoring anaesthetic depth with inhaled anaesthetic agents in the operating room but has not been evaluated as a monitor of sedation depth in the intensive care unit (ICU) setting with these agents. If BIS could predict sedation depth in ICU patients, patient disturbances could be reduced and oversedation avoided. Twenty ventilator-dependent ICU patients aged 27 to 80 years were randomised to sedation with isoflurane via the AnaConDa or intravenous midazolam. BIS (A-2000 XP, version 3.12), electromyogram activity (EMG) and Signal Quality Index were measured continuously. Hourly clinical evaluation of sedation depth according to Bloomsbury Sedation Score (Bloomsbury) was performed. The median BIS value during a 10-minute interval prior to the clinical evaluation at the bedside was compared with Bloomsbury. Nurses performing the clinical sedation scoring were blinded to the BIS values. End-tidal isoflurane concentration was measured and compared with Bloomsbury. Correlation was poor between BIS and Bloomsbury in both groups (Spearman's rho 0.012 in the isoflurane group and -0.057 in the midazolam group). Strong correlation was found between BIS and EMG (Spearman's rho 0.74). Significant correlation was found between end-tidal isoflurane concentration and Bloomsbury (Spearman's rho 0.47). In conclusion, BIS XP does not reliably predict sedation depth as measured by clinical evaluation in non-paralysed ICU patients sedated with isoflurane or midazolam. EMG contributes significantly to BIS values in isoflurane or midazolam sedated, non-paralysed ICU patients. End-tidal isoflurane concentration appeared to be a better indicator of clinical sedation depth than BIS.     

Propofol versus midazolam. Long-term sedation in the intensive care unit]

Sedative-analgesic treatment of patients on long-term artificial ventilation aims at protection from stress related to their disease or therapy. By stabilising both the patient's vital functions and psychological state this treatment may contribute to therapeutic success. The choice of drugs depends primarily on the nature and course of the underlying disease. Midazolam and propofol are available as hypnotics for short-term sedation during the post-operative period. The purpose of this study was to evaluate the effects of both agents on cardiovascular function, cortisol production, lipometabolism, and the recovery period following 24-h sedation. METHODS. Twenty female patients (mean body weight: 72 kg, mean age: 60 years) were randomly assigned to receive either midazolam or propofol over 24 h following major abdominal surgery. Balanced anaesthesia (halothane/O2/N2O/fentanyl) was administered for the surgical procedure. Assisted ventilation was used in all patients during the post-operative sedation period. Sedation depth was maintained at III-IV on the Ramsey scale. On arrival in the intensive care unit (ICU), an initial i.v. bolus of midazolam 0.1 mg/kg or propofol 1 mg/kg was followed by a continuous infusion (midazolam: 0.1 mg/kg.h; propofol: 2 mg/kg.h). Supplementary boluses of one-half the initial dose were given if required. Post-operative analgesia was achieved with 3 mg intravenous piritramide at 2-h intervals. A 7F Swan-Ganz catheter was inserted in the pulmonary artery and haemodynamic and biochemical parameters were monitored at 4-h intervals over 24 h starting 2 h after arrival in the ICU. Catecholamines were measured by high-pressure lipid chromatography (HPLC), cortisol by radioimmunoassay, midazolam by HPLC and ultraviolet detection, and propofol by HPLC and fluorescence detection. Data were calculated as means. The statistical analysis was performed according to the Mann-Whitney test, and significance was accepted for P less than 0.05. RESULTS. On administration of the propofol bolus at the onset of sedation, a decrease in blood pressure was particularly observed in patients with masked hypovolaemia, however, this decrease was easily controlled by volume administration. Independent of the type of sedation, the haemodynamic parameters remained unchanged throughout the observation period. At all times of measurement the mean heart rate was lower in the propofol group (90/min) when compared with the midazolam group (100/min), however, this difference did not reach significance. There were also no significant differences in cardiac index at all times of measurement, although it increased in both groups within the first 12 h by 0.6 l/min.min2. In both groups this increase was associated with a reduction in peripheral resistance and an increase in rectal temperature. To achieve the desired sedation depth, midazolam was administered at a mean dosage of 0.11 mg/kg.h and propofol at 1.9 mg/kg.h. Catecholamine levels decreased in both groups within the first 8 h: after 8 h of sedation the plasma levels of noradrenaline and adrenaline were 525 and 65 pg/ml, respectively, in the midazolam group and 327 and 51 pg/ml in the propofol group. (ABSTRACT TRUNCATED AT 400 WORDS)     

Propofol infusion with or without fentanyl supplementation for microlaryngoscopy

20 patients (ASA I to III) scheduled for microlaryngoscopy were randomly allocated to receive by infusion either 12-15 mg/kg/h propofol alone (group A) or 6-9 mg/kg/h with fentanyl supplementation (group B). All patients were premedicated with oral diazepam one hour before the procedure; they received an induction dose of 2 mg/kg propofol, preceded in group B by a bolus dose of fentanyl 1 microgram/kg. Significant hypotension was observed at induction in both groups to a similar degree (A:--26%; B:--30.2% compared to baseline). Placement of the laryngoscope induced sustained hypertension throughout the procedure in both groups (A: +28%; B: +20%) subsiding only at the removal of the instrument. Heart rate was never significantly altered. Arterial blood concentrations of propofol at induction reached high peak values (A: 16.82 +/- 8.52 micrograms/ml--B: 19.52 +/- 8.87 micrograms/ml--mean +/- SD) then remained stable throughout the procedure (A: 5.44 +/- 1.40 micrograms/ml--B: 2.91 +/- 1.06 micrograms/ml). At awakening, they were lower in group B (0.62 +/- 0.2 micrograms/ml) than in group A (1.17 +/- 0.55 micrograms/ml--p less than 0.05). Recovery was a little faster in group A (at the limit of significance). Though patients may present some excitation at awakening, recovery was usually very pleasant and characterized by swift return to consciousness, alertness and of all reflexes. We conclude that a propofol infusion is particularly suitable for microlaryngeal surgery. The addition of a narcotic agent allows reduction of the propofol dose range and does not alter recovery significantly. The proper dose of narcotic agent necessary to abolish cardiovascular reactivity to laryngoscopy must still be ascertained.     

Alfentanil and fentanyl sedation in infants and small children during cardiac catheterization

Thirty patients aged 1-23 mth received either alfentanil or fentanyl for the induction and maintenance of IV sedation during cardiac catheterization following oral flunitrazepam premedication (0.1 mg.kg-1). Patients breathed spontaneously 30 per cent oxygen in air. Both alfentanil and fentanyl abolished all reaction to pain and discomfort with minimal haemodynamic and respiratory changes. Induction doses of alfentanil and fentanyl were 20 +/- 6 and 2.5 +/- 1.1 (mean +/- SD) micrograms.kg-1, respectively, and maintenance requirements 30 +/- 12 and 1.5 +/- 0.6 micrograms.kg-1.h-1, respectively. These requirements were comparable among younger and older as well as cyanotic and acyanotic patients. The IV sedation described adds an effective method to the armamentarium of an anaesthetist working in the cardiac laboratory.     

Oral sedation with midazolam and diphenhydramine compared with midazolam alone in children undergoing magnetic resonance imaging

BACKGROUND: The purpose of this study was to compare the safety and efficacy of oral midazolam and midazolam-diphenhydramine combination to sedate children undergoing magnetic resonance imaging (MRI). METHODS: We performed a prospective randomized double-blind study in 96 children who were randomly allocated into two groups. Group D received oral diphenhydramine (1.25 mg x kg(-1)) with midazolam (0.5 mg x kg(-1)), and Group P received oral placebo with midazolam (0.5 mg x kg(-1)) alone. Sedation scores, onset and duration of sleep were evaluated. Adverse effects, including hypoxemia, failed sedation, and the return of baseline activity, were documented. RESULTS: Diphenhydramine facilitated an earlier onset of midazolam sedation (P < 0.01), and higher sedation scores (P < 0.01). In children who received midazolam alone, 20 (41%) were inadequately sedated, compared with 9 (18%) children who received midazolam and diphenhydramine combination (P < 0.01). Time to complete recovery was not significantly different between the two groups. CONCLUSIONS: Our study indicates that the combination of oral diphenhydramine with oral midazolam resulted in safe and effective sedation for children undergoing MRI. The use of this combination might be more advantageous compared with midazolam alone, resulting in less sedation failure during MRI.     

Propofol and midazolam for conscious sedation in a mentally retarded dental patient.

Conscious sedation was provided for a 21-yr-old mentally retarded and cardiovascularly compromised women who required dental extractions, by initially infusing propofol (3 mg/kg/hr), augmented with a bolus dose of intravenous midazolam (1 mg). After 45 min the propofol infusion rate was reduced to 1 mg/kg/hr. The patient remained well-sedated during the entire procedure and no adverse effects were experienced.     

Jet injector compared with oral midazolam for preoperative sedation in children

BACKGROUND: This study compared onset of sedation and satisfaction with two needleless jet injectors with the oral route for the administration of midazolam. METHODS: Forty-five children ages 1-6 years were randomly assigned to receive either 0.5 mg kg(-1) oral midazolam, 0.2 mg kg(-1) subcutaneous midazolam by J-Tip injector or 0.2 mg kg(-1) intramuscular midazolam by Bioject injector. After midazolam administration the children were monitored for oxygen saturation, heart rate and level of sedation (0, alert; 1, calm; 2, drowsy; 3, dozing; 4, asleep) every 2 min for 20 min by a physician blinded to the route of administration. Patient satisfaction, resistance to treatment, success of delivery, problems with separation, and acceptance of mask at the time of induction were evaluated after midazolam treatment. RESULTS: The Bioject showed a faster onset of sedation than either the J-Tip injector or the oral midazolam (P < 0.05). The children were significantly less satisfied with the Bioject and J-Tip administration vs oral midazolam (P < 0.05). There were no differences in resistance, success of delivery, problems with separation, mask acceptance, arterial oxygen saturation or heart rate. CONCLUSION: Despite children being less satisfied with Bioject injection of midazolam, the procedure is safe, effective and provides a more rapid onset of preoperative sedation in children than either the J-Tip injection or oral route.     

Propofol for long-term sedation in the intensive care unit. A comparison with papaveretum and midazolam

Thirty-seven patients with a wide range of illnesses were studied during mechanical ventilation of the lungs in an intensive care unit. Fifteen were sedated with a continuous propofol infusion, with analgesia provided by bolus doses of papaveretum. Twelve received a continuous infusion of papaveretum, supplemented by bolus doses of midazolam. The level of sedation was assessed every four hours and measurements were made of haemodynamic and respiratory variables. Levels of sedation were generally satisfactory in both groups. Six patients who received propofol required the use of muscle relaxants, because of their strong respiratory drives, to achieve synchronisation with the ventilator. There was no significant difference in respiratory or haemodynamic variables between the groups, but several patients required inotropic support because of their disease. There was no evidence of inhibition of adrenal steroidogenesis in the propofol group. Propofol can be a useful sedative agent in the intensive care unit, but sedative regimens should be tailored to individual patient requirements.