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.     

Respiratory management in a patient with severe tracheal stenosis caused by compression from the ascending aortic arch aneurysm

In cases of tracheal compression by a mediastinal mass or aortic aneurysm, muscle relaxant might induce fetal ventilatory failure. It is known to be valuable to keep spontaneous breathing in these cases. A 42-years-old woman complicated with Marfan syndrome had acute respiratory failure due to acute progression of tracheal stenosis caused by compression from the ascending and aortic pseudoaneurysm. After the induction of general anesthesia for video-assisted thoracic surgery (VATS) for high-pneumothorax, she was placed in lateral position. Suddenly it became difficult to ventilate her and her oxygenation saturation declined with bradycardia. We returned her to supine position and then could manage to ventilate her easier. But we could not maintain stable ventilation until her spontaneous breathing appeared. VATS was cancelled and she was brought in to the ICU after extubation. In the ICU she developed respiratory distress again soon and was reintubated under consciousness guided by bronchofiber scope. We managed successfully to keep spontaneous breathing intact under proper sedation by three sedative drugs; propofol, midazolam and morphine for 5 days until the next operation. We realized the importance of maintaining spontaneous breathing under proper sedation in a case of severe tracheal stenosis.     

Sedative and ventilatory effects of midazolam infusion: effect of flumazenil reversal

The purpose of this study was to evaluate the effects of flumazenil (1 mg iv) on the ventilatory response of premedicated patients receiving a continuous infusion of midazolam for sedation. After assessing baseline ventilatory function using a modified Read rebreathing method for determining hypercapnic ventilatory drive, 16 healthy outpatients were administered fentanyl, 50 μg iv, and midazolam 2 mg iv followed by a variable-rate midazolam infusion, 0.3–0.5 mg · min^?1. Upon termination of the midazolam infusion, serum midazolam concentrations were measured and ventilatory function was reassessed. Then, 10 ml of either saline or flumazenil (1 mg) were administered according to a randomized, double-blind protocol. Ventilatory function was subsequently measured at 5 min, 30 min and 60 min intervals after study drug. Compared with the baseline value, midazolam infusion reduced tidal volume and increased respiratory rate and alveolar dead space. However, midazolam did not decrease the slope of the CO₂-response curve. Flumazenil reduced the degree of midazolam-induced sedation and the decrease in tidal volume (P < 0.05), but not the change in resting respiratory rate. In some patients, the ventilatory response to hypercarbia actually decreased after flumazenil administration compared with the immediate prereversal (sedated) values. It is concluded that midazolam infusion, 0.43 mg · min^?1, did not impair CO₂-responsiveness. Flumazenil’s effect on central ventilatory drive was more variable than its reversal of midazolam-induced sedation.     

Compartment syndrome following intravenous regional anesthesia

PURPOSE: To present two cases of upper extremity compartment syndrome following intravenous regional anesthesia. CLINICAL FEATURES: Case 1: A 57-yr-old man presented for surgical release of a left-hand Dupuytren's contracture. The procedure was performed under iv regional anesthesia with 360 mg lidocaine and sedation with 150 microg fentanyl and 1.5 mg midazolam. Tourniquet time was 107 min at a pressure of 260 mmHg using three different tourniquet sites. Within minutes of tourniquet release, increased forearm muscle tension, hand anesthesia, pallor, and limited motor function developed. Serum CK and myoglobin levels rose. Myoglobinuria was present. Several fasciotomies and aggressive fluid therapy were performed. Patient made almost full recovery. Case 2: A 73-yr-old woman with controlled hypertension had Dupuytren fasciotomy of her right hand under iv regional anesthesia with 200 mg lidocaine and sedation using 75 microg fentanyl and 1.5 mg midazolam. Tourniquet time was 64 min at a pressure of 250 mmHg using three different tourniquet sites. The patient complained of pain at the iv site during injection of local anesthetic, third tourniquet inflation and after deflation of tourniquet. Thirty minutes after arrival in PACU, her fingers were bluish. She complained of pain and swelling of the forearm. Under general anesthesia, fasciectomy was performed. Myoglobin and CPK levels rose. CPK MB was high but troponin was negative. Three days later she developed pulmonary embolism. She was heparinized and subsequently discharged home. She recovered completely. CONCLUSION: Compartment syndrome may have a rapid and severe onset. Etiology of our cases is still not established. We postulate that increased tissue pressure may be the cause. The anesthesiologists must be aware of compartment syndrome during regional anesthesia.     

Clinical recovery time from conscious sedation for dental outpatients

For dental outpatients undergoing conscious sedation, recovery from sedation must be sufficient to allow safe discharge home, and many researchers have defined "recovery time" as the time until the patient was permitted to return home after the end of dental treatment. But it is frequently observed that patients remain in the clinic after receiving permission to go home. The present study investigated "clinical recovery time," which is defined as the time until discharge from the clinic after a dental procedure. We analyzed data from 61 outpatients who had received dental treatment under conscious sedation at the Hiroshima University Dental Hospital between January 1998 and December 2000 (nitrous oxide-oxygen inhalation sedation [n = 35], intravenous sedation with midazolam [n = 10], intravenous sedation with propofol [n = 16]). We found that the median clinical recovery time was 40 minutes after nitrous oxide-oxygen sedation, 80 minutes after midazolam sedation, and 52 minutes after propofol sedation. The clinical recovery time was about twice as long as the recovery time described in previous studies. In a comparison of the sedation methods, clinical recovery time differed (P = .0008), being longer in the midazolam sedation group than in the nitrous oxide-oxygen sedation group (P = .018). These results suggest the need for changes in treatment planning for dental outpatients undergoing conscious sedation.     

A case of long-term respiratory management following resection of a huge facial hemangioma]

A 49 year-old-woman was scheduled for resection of a huge hemangioma of the face and neck region. After the resection, severe edema developed on the tongue, larynx, and pharynx even leaving no space between the tracheal tube and these tissues. Prolonged respiratory management with endotracheal tube intubation was needed to maintain the upper airway for more than three weeks. Tracheostomy was performed 27 days after the operation. Two weeks later, the edema of the upper airway subsided. Thereafter her clinical course was uneventful, and she was discharged 22 days after the tracheostomy. Resection of a huge facial and neck hemangioma should be carefully managed as it can be followed by unexpected severe postoperative upper airway edema leading to suffocation.     

Intravenous sedation prior to peribulbar anaesthesia for cataract surgery in elderly patients

Purpose

To investigate if pre-block iv sedation using midazolam, alfentanil, or a midazolam-alfentanil combination minimizes pain, reduces pain recall, and attenuates haemodynamic responses to peribulbar block; and to determine other factors influencing oxygen saturation (SpO₂) following iv sedation.

Methods

In a randomized, double-blind, placebo-controlled study, 120 patients, mean age 73 yr, having cataract surgery with peribulbar anaesthesia, were randomized to receive either normal saline, 1 mg midazolam, 500 μg alfentanil, or 0.5 mg midazolam plus 250 μg alfentanil. Blood pressure (BP), heart rate (HR) and pulse oximetry readings were recorded before injection of the study drugs, immediately after completion of the peribulbar block, and 10 min after the block. Pain from the anaesthetic block was assessed immediately after the block and after surgery using a visual analog scale, and recall of pain was assessed by telephone on the day after surgery.

Results

Pain scores were low in all four groups. Midazolamalfentanil reduced pain perception, and all iv sedation used reduced pain recall. Midazolam reduced systolic BP; alfentanil ± midazolam reduced HR. All iv sedation reduced SpO₂ more than did saline, but not usually to a clinically important level. Nine patients had a SpO₂ S 90%; all had received alfentanil with or without midazolam. It was not possible to predicoxygen saturation levels by any factors other than iv sedation and baseline SpO₂ levels.

Conclusion

Intravenous sedation with midazolam or alfentanil or in combination reduced pain perception, pain recall, and haemodynamic responses from peribulbar anaesthesia. Fifteen percent of patients given alfentanil developed clinically important oxygen desaturation. The use of fine gauge needles combined with slow injection of anaesthetic solution causes minimal discomfort, and routine iv sedation may be unnecessary.     

Case of caesarian section in a patient with a giant mediastinal tumor

Administering anesthesia to a patient with a mediastinal tumor may lead to respiratory difficulty with relatively high morbidity and mortality. A 35-year-old pregnant woman with a large mediastinal tumor was scheduled for caesarian section. Chest roentgenography revealed a large mediastinal tumor. General anesthesia was selected to cope with possible worsening of dyspnea and coughing which could be more likely to occur during spinal anesthesia. Mechanical ventilation caused no trouble. When she started spontaneous breathing after the operation, dyspnea suddenly developed and SpO2 began to fall. Emergency bronchofiberscopy revealed almost total occlusion of the right main bronchus due to extrinsic compression.     

Anterograde amnesia as a possible postoperative complication of Midazolam as an agent for intravenous conscious sedation

Anterograde amnesia is often considered to be a beneficial effect of intravenous conscious sedation. The recently introduced benzodiazepine, midazolam, has associated with its administration a significant anterograde amnesic period. In the case presented here, a healthy young female presented for third molar extraction under midazolam conscious sedation and local anesthesia. After uncomplicated removal of the teeth and clinically adequate recovery from sedation, it was noted that the patient had swallowed the postsurgical gauze packs. Efforts at recovery of the gauze packs were futile. Follow-up discussion with the patient revealed a complete lack of recall of all events occurring for up to an hour or more after the administration of intravenous midazolam. The need for written and oral postoperative instructions to both the patient and his/her escort is emphasized.     

Airway obstruction due to late-onset angioneurotic edema from angiotensin-converting enzyme inhibition

PURPOSE: Angioneurotic edema is a well-documented complication of angiotensin-converting enzyme inhibitors (ACEI). We report a case of acute airway obstruction from a late-onset, probable ACEI-related angioneurotic edema and its subsequent management. CLINICAL FEATURES: A 48-yr-old obese man presented for transurethral resection of a bladder tumour (TURBT). His past medical history included hypertension controlled with hydrochlorothiazide and quinapril which had been started 13 mo earlier. Previous surgery was uncomplicated. Midazolam was used for premedication and for intraoperative sedation together with fentanyl and propofol. After uneventful spinal anesthesia with bupivacaine, operation and recovery, he was transferred to the floor. Five hours later he developed severe edema of his face, tongue and neck, with drooling, that progressed into airway obstruction and respiratory arrest. Ventilation was restored via immediate cricothyroidotomy, and a subsequent tracheotomy was completed uneventfully in the operating room. His serum C1 esterase inhibitor levels at 1, 5 and 23 days later were normal. The angioneurotic edema was attributed to the ACEI treatment. The edema resolved after 48 hr, and further follow-up was unremarkable. CONCLUSION: This observation is consistent with other reports that angioneurotic edema from ACEI can occur many months after the initiation of treatment. This can involve the airway and may produce life-threatening respiratory compromise. Physicians should be aware of this association and the possible need for immediate surgical intervention for the establishment of an airway in case of worsening edema or respiratory arrest.     

COMPARISON OF MIDAZOLAM BY MOUTH AND DIAZEPAM I.V. IN OUTPATIENT ORAL SURGERY

In a randomized double-blind, parallel groups study, 40 patientsundergoing surgical removal of impacted 3rd molar teeth receivedeither midazolam 15 mg orally followed at 35 min by i.v. saline,or oral placebo followed at 35 min by i.v. diazepam 10 mg (Diazemuls).Rapid onset of sedation was seen after midazolam, while thepattern and duration of postoperative sedation, as measuredby standard psychometric tests, indicated slower recovery aftermidazolam than after diazepam. Ratings by the surgeon indicatedsuperior anxiolysis following midazolam and significantly morepatients expressed a preference for oral midazolam sedation.Significant, comparable anterograde amnesia was seen with bothtreatments. No significant cardiovascular complications occurredwith either treatment. The findings indicate that rapidly actingoral benzodiazepines such as midazolam provide safe, effectalternatives to i.v. diazepam for conscious sedation in outpatientsundergoing minor surgical procedures.     

SEDATION AND RESPIRATORY MECHANICS IN MAN

The effects of sedation with halo thane, enflurane or midazolamon respiratory mechanics and lung volumes were studied in younghealthy volunteers, in the supine position. Functional residualcapacity increased with halothane sedation, but was unchangedwith sedation produced by enflurane or midazolam. Sedation withhalothane and enflurane, but not midazolam, tended to increaselung static recoil pressure. Total lung capacity was decreasedduring sedation with midazolam. No evidence was found that sedationwith these three agents increased airway resistance. These findingsimply that changes in respiratory mechanics induced by the residualeffects of anaesthetic agents are unlikely to contribute significantlyto the impairment in pulmonary gas exchange which may occurin the period immediately after operation.     

Development of takotsubo cardiomyopathy with severe pulmonary edema before a cesarean section

Takotsubo cardiomyopathy is an acute syndrome involving apical ballooning and consequent dysfunction of the left ventricle. Most cases of left ventricular dysfunction resolve within 1 month. We present the case of a 40-year-old woman who developed severe heart failure caused by takotsubo cardiomyopathy with severe left ventricular dysfunction during the perinatal period. Because of the presence of multiple myomas, she was scheduled to undergo a cesarean section under general anesthesia. However, after induction of general anesthesia, she had to be awakened because of the presence of a difficult airway. Because she exhibited insufficient oxygenation, she was transferred to the emergency center. Upon hospital admission, she expectorated large amounts of pink sputum, indicating severe pulmonary edema. Cesarean section was performed immediately. Echocardiography revealed severe left ventricular dysfunction. Full recovery of cardiac function required almost 1 month, after which she was discharged from the hospital without further complications. This is the first reported case of takotsubo cardiomyopathy induced by a failed intubation during a scheduled cesarean section. Takotsubo cardiomyopathy usually shows a good prognosis, but if this myopathy develops during the perinatal period, it can worsen because of excessive preload following the termination of fetoplacental circulation.     

A case of pharyngolaryngeal edema after posterior occipito-cervical operation

A 70-year-old female developed respiratory failure due to pharyngolaryngeal edema after posterior occipito-cervical fusion. She had a history of total thyroidectomy with bilateral neck dissection for advanced thyroid cancer associated with multiple lung metastases. However, her general condition was good, and she was not in cachexia. Her pulmonary function test revealed %VC of 54% and %FEV1.0 of 79%. This posterior occipito-cervical fusion was necessary for pain relief. Twenty-four hours after surgery she suddenly showed dyspnea, requiring tracheal intubation, and was supported by mechanical ventilation. The pharyngolaryngeal edema was recognized with bronchoscopy from the lower larynx with arytenoid region to nasal choana. In several days she recovered from pharyngolaryngeal edema and was extubated. She was discharged from ICU after close observation for 24 hours after extubation. She developed respiratory distress again due to difficulty in sputum expectoration, resulting in emergency tracheostomy an the floor at midnight. In this case, pharyngolaryngeal edema may have been caused by disturbance of lymphatic flow due to posterior occipito-cervical fusion in a patient with a past history of bilateral neck dissection. We also reviewed the literature in this report.     

Reversal of central benzodiazepine effects by intravenous flumazenil.

The purpose of this study was to determine the efficacy of flumazenil in safely expediting patient recovery from benzodiazepine sedation. This double-blind, randomized, placebo-controlled study involved 30 patients who received conscious sedation induced by intravenous midazolam given for a dental surgical procedure. Patients who received flumazenil were rated significantly more alert than were placebo-treated patients at 5 and 15 min following test drug administration. They also had significantly superior scores on the digital symbol substitution test and on tests in a comprehensive modified neurological examination 5 min after receiving flumazenil. Group differences were not as impressive on recall and recognition tests. However, flumazenil patients scored somewhat more favorably than the placebo group patients in identifying simple objects they had been shown during the observation period following surgery. Flumazenil appears to be a promising drug for reversing midazolam conscious sedation.     

Banked autologous blood for caesarian section

Experience with the use of banked autologous blood in five patients undergoing elective caesarian section showed that two patients developed painless uterine contractions during phlebotomy, and a third delivered an infant who developed severe respiratory distress. The other two patients had no complications and delivered healthy infants. Caution is needed before recommending the use of this technique in obstetric practice.     

Steroid replacement therapy for severe heart failure after Norwood procedure

A 15-day-old neonate demonstrated severe heart failure and capillary leak syndrome after undergoing a Norwood procedure for hypoplastic left heart syndrome. Because she developed severe subcutaneous edema and baseline blood cortisol was low, we suspected relative adrenal insufficiency. After 18 days of dexamethasone administration, her hemodynamics and respiratory function improved, and she was successfully extubated and discharged from hospital. When hemodynamics are unstable in neonates after major cardiac surgery, relative adrenal insufficiency and steroid replacement should be considered.     

A single dose of fentanyl and midazolam prior to Cesarean section have no adverse neontal effects

PURPOSE: Analgesia and sedation, routinely used as adjunct medications for regional anesthesia, are rarely used in the pregnant patient because of concerns about adverse neonatal effects. In an effort to obtain more information about maternal analgesia and sedation we studied neonatal and maternal effects of iv fentanyl and midazolam prior to spinal anesthesia for elective Cesarean section. METHODS: In this double-blinded, randomized, placebo-controlled trial, 60 healthy women received either a combination of 1 microg x kg(-1) fentanyl and 0.02 mg x kg(-1) midazolam intravenously or an equal volume of iv saline at the time of their skin preparation for a bupivacaine spinal anesthetic. Sample size was based on a non-parametric power analysis (power > 0.80 and alpha = 0.05) for clinically important differences in Apgar scores. Fetal outcome measures included Apgar scores, continuous pulse oximetry for three hours, and neurobehavioural scores. Maternal outcomes included catecholamine levels, and recall of anesthesia and delivery. RESULTS: There were no between-group differences of neonatal outcome variables (Apgar score, neurobehavioural scores, continuous oxygen saturation). Mothers in both groups showed no difference in their ability to recall the birth of their babies. CONCLUSIONS: Maternal analgesia and sedation with fentanyl (1 microg x kg(-1)) and midazolam (0.02 mg x kg(-1)) immediately prior to spinal anesthesia is not associated with adverse neonatal effects.     

Reversal of prolonged sedation using flumazenil in critically ill patients

Thirteen critically ill patients received flumazenil after multiple doses, or an infusion, of midazolam was used as part of a sedation regimen to facilitate intensive care. All patients remained excessively sedated after the midazolam was stopped for 6 hours or longer. An improvement in conscious level occurred in eight patients (61%). In four of these eight patients, the duration of action of flumazenil necessitated its continued administration by an infusion to maintain the improvement in conscious level. The dose of flumazenil required each hour was less than estimated previously; this indicates that it may be subjected to similar alterations of elimination as those described for midazolam. Flumazenil appears to be a useful drug for the reversal of prolonged benzodiazepine sedation but repeated bolus doses or an infusion are needed if significant accumulation of benzodiazepines has occurred.     

Severe airway obstruction relieved by sedation using sevoflurane in a pediatric patient with tracheobronchomalacia

A 3-month-old baby with trisomy 18 syndrome was scheduled for tracheostomy under general anesthesia because of the prolonged tracheal intubation. Immediately after transferring the patient to the operating table, the patient suddenly began crying and coughing, resulting in severe hypoxia. The patient's lungs could not be ventilated by manual and positive pressure ventilation, and airway obstruction could not be relieved until the respiratory effort spontaneously decreased. We started to administer sevoflurane on the recommendation of pediatricians who had successfully treated the patient with sedation using either midazolam or trichlorethylphosphate in similar situations. After sevoflurane administration, the sedated patient never developed the respiratory effort, and the lungs could be ventilated by manual and positive pressure ventilation without difficulty. The patient was diagnosed as tracheobronchomalacia as a result of intraoperative flexible bronchoscopy performed through tracheostomy tube, revealing significant narrowing of both the trachea and mainstem bronchus lumens. Sedation using sevoflurane may be helpful in maintaining airway patency in the pediatric patient with tracheobronchomalacia.