Facilitation of fiberoptic nasotracheal intubation with magnesium sulfate: A double-blind randomized study.

BACKGROUND: A double-blinded, prospective, and randomized study was designed to determine the efficacy and tolerability of intravenous (IV) magnesium sulfate (MgSO4) to facilitate fiberoptic bronchoscopic (FOB) nasotracheal intubations. PATIENTS AND METHODS: A total of 120 patients scheduled to undergo elective awake fiberoptic nasotracheal intubation, while they were anesthetized for elective surgery were randomly allocated to one of three groups: The control Group S (n = 40) received 100 ml (50 ml 0.9% saline + 50 ml paracetamol) was infused in 10 min and direct IV 5 ml 0.9% normal saline, Group MD (n = 40): Received midazolam IV in a dose of 0.07 mg/kg in 5 ml 0.9% normal saline and 100 ml 0.9% was infused in 10 min and Group MS (n = 40): IV 45 mg/kg MgSO4 10 min in 100 ml of 0.9% normal saline through 10 min and direct IV 5 ml 0.9% normal saline.
RESULTS: Time required for nasotracheal intubation was significantly less in group Groups MD and MS, as compared with the control group, but not significant between the two groups. (Group MD: 9.05 + 1.95 min, Group MS 3.75 + 0.75 min and Group S 16.85 + 1.7 min). However, the number of fiberoptic intubation was significantly more in the MD and MS groups, as compared with the control group. Easy intubation (control group: 0, Group MD: 25 and Group MS: 35), moderate difficulty (control group: 5, Group MD: 12 and Group MS: 4) and difficult (control group: 35, Group MD: 3 and Group MS: 1). Procedure adverse events were significantly lower in Group MS. None of the patients in Group MS had procedure hypoxia, but it occurred in 10 patients of Group MD and 20 patients in Group S. Six patients in Group S and two in Group MD had procedure apnea whereas, none of the patients in the MS group experienced this. After medication and just before intubation heart rate and mean arterial pressure were significantly less in Groups MD and MS, as compared to the control group (Group MD: 77 + 7.7 beat/min, Group MS: 70 + 5.6 beat/min and Group S: 80 + 7.8 beat/min) (Group MD: 90 + 8.5 mmHg, Group MS: 80 + 8.1 mmHg and Group S: 105 + 10.5 mmHg). This difference however, significant between Group MD and Group MS.
CONCLUSION: Intravenous MgSO4 improved awaken FOB intubation without adverse hemodynamic or respiratory effects.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Although passage of a tracheal tube over a fiberoptic bronchoscope has improved the ability to manage a difficult airway, however, this technique doesn’t ensure successful intubation,[12] especially after topical anesthesia of the tongue and pharynx with lidocaine spray, patients cannot tolerate fiberoptic bronchoscopy with discomfort.[3] The various audits of bronchoscopic practice have reported mortality rates of 0.01-0.5% and major complication rates of 0.08-5%, respectively.[4] Most of deaths and major complications have been related to the sedative regimen used.[567] This has led to an increased awareness of the need for a satisfactory sedative regimen for fiberoptic usage.[8910]

The sedative drugs that were commonly used are opioids and benzodiazepine.[1112] Magnesium (Mg) plays a fundamental role in many physiological process, for example neuronal activity, muscular contraction, and control of vasomotor tone. Mg is known to possess muscle relaxing effects, mostly by reducing, acetylcholine release, and it seems to have antinociceptive and anesthetics effects.[131415]

We hypothesized that the administration of magnesium sulfate (MgSO4) could facilitate fiberoptic nasotracheal intubations.

PATIENTS AND METHODS

This study was carried out after obtaining approval from Institutional Ethical Committee. A written informed consent was obtained from 130 patients, ages ranged between 22 and 66 years of both sex and scheduled to undergo elective awake fiberoptic nasotracheal intubation while they were anesthetized for elective surgery from January 2013 to December 2013 patients, who declined to participate or had known abnormal laryngeal structures (e.g. tumors), infectious and toxic conditions of the neck and airway, and traumatic conditions of the neck other than cervical spine fractures or dislocations were excluded from the study.

During the preparation visit, an evaluation of the anatomy of the airway was done, according to Mallampati score classification.[16] Furthermore, the data of awake intubation were explained. Peripheral cannula was inserted. Patients were classified into three groups (40 patients in each group).

Group S (n = 40): Received 100 ml (50 ml 0.9% saline + 50 ml paracetamol) was infused in 10 min and direct intravenous (IV) 5 ml 0.9% normal saline

Group MD (n = 40): received midazolam IV in a dose of 0.07 mg/kg[17] in 5 ml 0.9% normal saline and 100 ml 0.9% was infused in 10 min

Group MS (n = 40): IV 45 mg/kg MgSO4 10 min in 100 ml of 0.9% normal saline through 10 min and direct IV 5 ml 0.9% normal saline.

All patients received 1 mg atropine sulfate IV and Afrin nasal decongestant drops in the right nostril. Topical anesthesia was achieved by nebulizer for 10 min using 10 ml lidocaine 2%.

After preparation of patients, nastroacheal tube (8 mm) was inserted through the right nostril into the oropharynx, and then well lubricated fiberoptic bronchoscope (STARZ 5-4 mm) was passed through the tube and manipulated to identify the epiglottis and cords. The bronchoscope was advanced into the trachea to the level of the carina, then the tube threaded over it.

The degree of difficulty of intubation was classified by an experienced observer according to the following.[1]

Not difficult

If no manipulation of the tip of the scope was needed.

Moderately difficult

Moderate manipulation of the bronchoscope in all directions was necessary to locate the cords.

Difficult

It would be difficult to identify the cords extensive manipulation of the bronchoscope in all directions with change in position of the operator.

Furthermore, the intubations time was measured, which is the time from insertion of the bronchoscope to completion of intubation. All the medications were prepared by an anesthesiologist who was not involved in any other aspect of the study. All syringes were identical and had similar volumes of the test and placebo solutions. The investigator who administered the drug, the anesthesiologist who performed the procedure and the patients, were unaware of the group allocated and the drug that was received by the patient.

Monitoring

Mean arterial pressure (MAP), heart rate and oxyhemoglobin saturation (PO2) through pulse oximetry were monitored.

Hypoxemic episodes were defined as SPO2 <90% and lasting ≥10 s. Apnea was defined as the absence of spontaneous respiration for >15 s. If hypoxemia or apnea occurred, spontaneous respiration was encouraged by vocal or tactile stimuli.

If hypotension occurred (MAP decreased ≥30% of baseline, 6 mg ephedrine was administrated. If heart rate decreased to <50 beat/min, 0.6 mg atropine sulfate IV was given.

In all patients to blow the secretions away from the tip of fiberoptic bronchoscopic (FOB), oxygen was insufflated through the suction port of the instrument (2 L/min).

The tip of FOB was immersed in warm saline (37°C) 1 min prior to insertion to prevent fogging.

Statistical analysis

The sample size was calculated to be N = 40 based on the following considerations: 95% confidence level, 80% power of the study. Equal size of the studied groups the estimated outcome to range between 50% and 80% between the studied groups. Statistical analysis was performed using one-way analysis of variance for normally distributed parametric data. Time required for nasotracheal intubation, procedure adverse events (case of FOB intubations, hypoxia, and apnea) were analyzed by the Kruskal-Wallis test followed by the post hoc multiple comparison tests using the Dunnett method. P < 0.05 was considered as statistically significant.

RESULTS

A total of 130 patients were randomized into the study, of which ten patients were excluded. Of these, six patients had inadequate anesthesia and were given general anesthesia. Four patients went into active vomiting leading to prolong the procedure time. Statistical analysis was performed in the remaining 120 patients, 40 in each group.

There was no statistically significant difference between the groups as regard to patient demography and hemodynamics before the procedure [Tables 1 and 3]. The time required for nasotracheal intubation was significantly less in the Groups MD and MS, as compared with the control Group S. (Group MD: 9.05 + 1.95 min, Group MS: 3.75 + 0.75 min and Group S: 16.85 + 1.7 min). This difference however, significant between Groups MD and MS [Table 2]. The number of fiberoptic intubation was significantly more in the MD and MS groups, as compared to the control group. Easy (control group: 0, Group MD: 25 and Group MS: 35), moderate difficulty (control group: 5, Group MD: 12 and Group MS: 4) and difficult (control group: 35, Group MD: 3 and Group MS: 1) [Table 3]. Procedure adverse events were significantly lower in Group MS as compared to Group S and Group MD. 20 patients in Group S and ten in Group MD had procedure hypoxia, six patients in Group S and two in Group MD had procedure apnea whereas, none of the patients in the MS group experienced this [Table 3]. After medication and just before intubation heart rate was significantly less in the group in Groups MD and MS, as compared to the control group (Group MD: 77 + 7.7beat/min, Group MS 70 + 5.6 beat/min and Group S 80 + 7.8 beat/min). This difference, however, significant between Group MD and Group MS. MAP was significantly less in the groups MD and MS, as compared to the control group. (Group MD: 90 + 8.5 mmHg, Group MS 80 + 8.1 mmHg and Group S 105 + 10.5 mmHg). This difference however, significant between Groups MD and MS.

Table 1

Demographic data

Table 3

Procedure adverse events

Table 2

Intubation time (min)

DISCUSSION

Midazolam is a water soluble benzodiazepine with an elimination half-life of about 2 h and a rapid onset and a short duration of action in normal subjects.[17] Its primary metabolite is pharmacologically active. Elderly patients are extremely sensitive to midazolam and extreme caution is recommended with its in elderly.[3] Midazolam caused respiratory depression. With low doses the decreased tidal volume is compensated for by an increased respiratory rate, with larger doses, this compensation mechanism is lost, and hypoxemia or apnea may occur.[456]

A total of 1615 adverse events after use of Midazolam have been reported to the department of health and human services as a June 27, 1989. The dose of Midazolam report eddy administrated most often ranged from 1 to 10 mg. These reactions ranged from Hiccup to death. The most frequently reported adverse reaction was apnea, hypoxia or cyanosis. Fifty times reported from a total of 86 deaths occurred in the adverse drug reaction reported in US.[8]

This study shows that IV MgSO4 45 mg/kg improved awaken FOB intubation without adverse hemodynamic or respiratory effects.

The mechanism of action of Mg appears to be multifactorial. It has analgesic, anesthetic and muscle relaxant effects.[141516]

Magnesium is the 4th most abundant cation in the body and the 2nd most an abundant intracellular cation.[161718] It acts as a natural Ca+ = antagonist regulating Ca++ access into the cell[19] it has the potential to treat and prevent pain by acting as an antagonist at N-methyl-D-aspartate receptors.[20]

The study of tramer et al.[20] showed the value of Mg as adjuvant in postoperative analgesia. Patients receiving Mg required less morphine had less discomfort and sleep better during 1st 48 h than those receiving morphine alone. Three respiratory depressions occurred in the group receiving morphine only versus none in the group treated with morphine and Mg. Koini et al.[21] have reported similar results, with a reduced analgesic use both intra- and post-operatively.

Magnesium is considered to be a muscle relaxant like agent. Neuromuscular transmission isolated by reduction in the release of acetylcholine at motor nerve terminal.[15] A clinical study demonstrated that a rapid infusion of MgSO4 (50 mg/kg) can re-establish relevant degree of muscle paralysis in patients who have just recovered from nondepolarizing blocking agents.[2223]

In patients with Tetanus MgSO infused at doses providing serum concentrations of 2-4 mmol/L allowed good control of spasm and muscle rigidity.[24]

Magnesium decreases the amount of acetylcholine released from motor nerve terminal, leading to diminished exact ability of the muscle fiber itself and reduction in the amplitude of the end plate potential. It therefore, potentiates the nondepolarizing neuromuscular blocking agents.[2526]

Magnesium decreases catecholamine release from the adrenal medulla and adrenergic nerve endings it obtunds the pressor response to laryngoscopy and intubation.[16]

Choi et al.[25] concluded that IV Mg SO4 reduced propofol infusion requirements. It could be related to the sedative effect of Mg. Mg has been reported to produce general anesthesia and to enhance the activity of local anesthetic agents.[27]

A narcotic state inhuman being undergoing surgical operations was achieved in a study by Peck and Meltzer who reported three patients. Undergoing hernioplasty under attempted anesthesia by MgSO4 infusion.[18]

CONCLUSION

Fiberoptic bronchoscopic tracheal intubation in MgSO4 group was easier faster and without hemodynamic or respiratory adverse effects as compared with midazolam group.

Hence, we recommend IV MgSO4 to facilitate awaken FOB tracheal intubations.