|Year : 2016 | Volume
| Issue : 4 | Page : 606-611
Control of autonomic dysreflexia in patients with high level of chronic spinal cord injury during cystoscopy
Ibrahim A Nasr, Khaled M Elnaghy
Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||01-Nov-2015|
|Date of Acceptance||22-May-2016|
|Date of Web Publication||12-Jan-2017|
Ibrahim A Nasr
Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, P.O. 64399 Riyadh 11536, KSA
Source of Support: None, Conflict of Interest: None
Autonomic dysreflexia (AD) is a clinical emergency that frequently occurs in patients with spinal cord injury (SCI) during cystoscopy. It should be treated by removing the stimulus and by medications. We aimed in this study to evaluate the effect of adding magnesium sulfate to dexmedetomidine infusion to control AD in high-level chronic SCI patients during cystoscopy.
Patients and methods
Forty patients with chronic SCI at the level of T6 or above scheduled for cystoscopy were randomly divided into two groups: the dex group, in which the patients received dexmedetomidine infusion 1 µg/kg for 10 min, followed by 0.5 µg/kg/min; and the Mg group, in which patients received a single i.v. dose of magnesium sulfate 50 mg/kg in addition to the same infusion of dexmedetomidine. Blood pressure (BP) and heart rate (HR) were recorded for each patient, and serum magnesium, epinephrine, and norepinephrine levels were estimated preoperatively, intraoperatively, and postoperatively.
Results showed a significant elevation in intraoperative BP in the Dex group 10 min after cystoscopy and persisted for 20 min compared with the presedation level in the same group and with the same readings in the Mg group. HR dropped down in the Dex group 15 min after cystoscopy and persisted for 15 min compared with the presedation reading in the same group and with the same readings in the Mg group. Serum magnesium was significantly higher intraoperatively and postoperatively in the Mg group, whereas serum epinephrine and serum norepinephrine were significantly higher intraoperatively and postoperatively in the Dex group compared with the presedation level in the same group and with the same readings in the Mg group. Seven patients (35%) in the Dex group experienced a dysreflexic episode [increase in systolic blood pressure (SBP) 30 mmHg or more compared with the presedation reading]; two of them showed elevation of SBP more than 160 mmHg and needed to be treated. On the other hand, only one patient in the Mg group (5%) experienced a dysreflexic episode (SBP 135 mmHg) with no need for medication.
Addition of a single i.v. dose of magnesium sulfate to dexmedetomidine infusion provides a better control of BP and HR, and reduces the incidence of AD during cystoscopy in patients with high level of chronic SCI.
Keywords: autonomic dysreflexia, dexmedetomidine, magnesium sulfate
|How to cite this article:|
Nasr IA, Elnaghy KM. Control of autonomic dysreflexia in patients with high level of chronic spinal cord injury during cystoscopy. Ain-Shams J Anaesthesiol 2016;9:606-11
|How to cite this URL:|
Nasr IA, Elnaghy KM. Control of autonomic dysreflexia in patients with high level of chronic spinal cord injury during cystoscopy. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2017 Oct 22];9:606-11. Available from: http://www.asja.eg.net/text.asp?2016/9/4/606/198256
This work has been carried out in Sultan Bin Abdulaziz Humanitarian City, Riyadh, Kingdom of Saudi Arabia.
| Introduction|| |
Autonomic dysreflexia (AD) is a clinical emergency that frequently occurs in patients with a chronic spinal cord injury (SCI) at the level of T6 or above ,. The acute episode of AD is characterized by an acute elevation of arterial blood pressure (BP), which may reach 300 mmHg, and bradycardia [heart rate (HR) may drop down to 30 beat/min], with a high risk for intracranial hemorrhage, retinal detachment, seizures, and death ,,,.
Irritation of the urinary bladder is a common stimulus that triggers AD ,. Physiologically, AD is caused by a massive sympathetic discharge triggered by either a noxious or non-noxious stimulus originating below the level of the SCI .
Patients with chronic injury to the spinal cord are known to have decreased levels of circulating catecholamines and an increased sensitivity to norepinephrine . In addition, plasma norepinephrine levels rise markedly during episodes of AD .
Management of AD requires removal of the precipitating stimulus when possible, and, if necessary, pharmacological intervention. Magnesium sulfate can control catecholamines-induced hypertensive crises through several antiadrenergic mechanisms and mediate direct vasodilator effect on vessels walls . Moreover, dexmedetomidine is a highly selective α2-adrenergic agonist that can reduce circulating catecholamine levels, which results in sympatholysis and anxiolysis with respiratory preservation .
In this study, we evaluated the effect of adding a single i.v. dose of magnesium sulfate to dexmedetomidine infusion to control AD in chronic SCI patients (level of T6 or above) undergoing urological procedures under moderate sedation [Monitored Anesthesia Care (MAC)].
| Patients and methods|| |
This prospective, randomized, double-blinded study was conducted at Sultan Bin Abdulaziz Humanitarian City (the largest rehabilitation hospital in the Kingdom of Saudi Arabia) over a period of 8 months (from December 2014 to July 2015). In total, 40 patients of both sexes, aged between 16 and 45 years, belonging to the American Society of Anesthesiologist physical status II, with paraplegia secondary to chronic SCI at level of T6 and above, and scheduled to undergo elective cystoscopy and Botox injection for urinary bladder enlargement under moderate sedation (MAC) were included in the study. The approval for the study was granted by the Research Ethics Committee. All the patients signed a written consent before participation in the study.
The study parameters were designed to detect the hemodynamic changes (arterial BP and HR) and hormonal changes (serum epinephrine and norepinephrine) in response to urinary bladder stimulation under moderate sedation with dexmedetomidine infusion alone compared with its combination with magnesium sulfate. In the latter group of patients, serum magnesium level was monitored to ensure that it reached the therapeutic level and to avoid magnesium overdose.
On arrival to the preanesthesia area, an i.v. line was established and 6 ml of blood was withdrawn as a presedation sample (S1); then, an infusion of Ringer’s lactate solution was started at the rate of 7 ml/kg/h. Routine monitoring was immediately started with ECG, pulse oximetry, and noninvasive BP monitoring every 5 min, with very closely observing the conscious level and respiratory pattern. Then the patients were randomly allocated by using a computer-generated random list to one of the two parallel groups.
- The Dex group (n=20): patients were given dexmedetomidine infusion, which was started in the preanesthesia room at a rate of 1 mg/kg over 10 min as a loading dose, followed by continuous infusion with 0.5 mg/kg/h till the end of the procedure. Patients in this group were given 10 ml of i.v. normal saline over 10 min as placebo.
- The Mg group (n=20): patients were given a single i.v. bolus of magnesium sulfate at a dose of 50 mg/kg over 10 min, in addition to dexmedetomidine infusion, which was started in the preanesthesia room at a rate of 1 mg/kg over 10 min as a loading dose, followed by continuous infusion with 0.5 mg/kg/h till the end of the procedure.
Patients with the following criteria were excluded from the study: hypermagnesemia, a known allergy to magnesium sulfate, any degree of heart block, hypertension or diabetes mellitus, cardiovascular dysfunction, renal or hepatic disease, endocrine or metabolic disease, and chronic treatment with calcium channels blockers.
Drugs for injection and infusions were prepared by an anesthesia technician who was not involved in the study. Patients, the attending anesthesiologist, and the operating-room and recovery-room personnel were blinded to patient allocations.
In the operating theater, ECG, HR, noninvasive BP, and oxygen saturation (SpO2) were monitored, and baseline values were recorded. Then, all patients were given 2–3 mg of midazolam i.v. in the lithotomy position to keep the sedation score between 2 and 3 according to the sedation scale criteria ([Table 1]).
Arterial BP and HR were recorded at the moment of cystoscope introduction (0 min) and every 5 min till the end of procedure, and then for 1 h postoperatively in the recovery room. Second blood sample (S2) was withdrawn 20 min after the cystoscope introduction.
BP higher than 160/100 was treated with hydralazine 5 mg i.v. bolus and HR lesser than 40 beats/min was treated with atropine 0.4 mg i.v. bolus dose.
After the end of the procedure, patients were transferred to the recovery room under the same monitoring. Last blood sample (S3) was withdrawn in the recovery room 1 h after cystoscope removal. The three blood samples were sent to the laboratory to measure preoperative, intraoperative, and postoperative serum magnesium, serum epinephrine, and serum norepinephrine.
Data were collected and analyzed using a statistical software package for Windows (Graph Pad In Stat, version 3.00; Graph Pad Software Inc., San Diego, California, USA) and presented as mean±SD, number, percentage, or ratio as appropriate. A power analysis of α=0.05 and β=0.90 showed that 15 patients were required per study group to detect a 30% difference in the incidence of AD between the two groups. Groups were compared using the parametric or the nonparametric versions of analysis of variance, followed by appropriate post-hoc analysis if significance was detected. Nominal data were compared by using the χ2-test or alternatively by using the Fisher’s exact test, as appropriate. P values less than 0.05 were considered significant.
| Results|| |
Forty patients completed the study. There were no significant differences regarding age, body weight, sex, duration of surgery, and duration of sedation between the two study groups, as shown in [Table 2].
Both groups showed a significant reduction in systolic blood pressure (SBP) and HR after midazolam injection (before sedation vs. before cystoscopy), without significant differences between the two groups, as shown in [Table 3].
|Table 3: Systolic blood pressures, diastolic blood pressures in mmHg, and heart rates in beats/min as shown in the study groups|
Click here to view
The results showed a significant elevation in SBP and diastolic BP in the Dex group compared with the presedation reading in the same group and with the same reading in the Mg group, which started after 10 min of cystoscopy and persisted till 25 min of the procedure (P<0.05). On the other hand, the HR showed a significant drop in the Dex group after 15 min of cystoscopy compared with the presedation level and became significant compared with the Mg group after 20 min of cystoscopy and persisted for 10 min (P<0.05), as shown in [Table 3].
The Mg group showed a significant elevation in serum magnesium in intraoperative sample (S2) and postoperative sample (S3) compared with S2 and S3 in the Dex group and preoperative sample (S1) in the Mg group (P<0.0001). Whereas the Dex group showed a significant elevation in serum epinephrine and norepinephrine in S2 and S3 compared with S2 and S3 in the Mg group and S1 in the Dex group (P<0.0001), as shown in [Table 4].
|Table 4: Serum magnesium (mmol/l), serum epinephrine (pg/ml) and serum norepinephrine (pg/ml) levels in the study groups|
Click here to view
Seven patients out of 20 (35%) in the Dex group suffered from a dysreflexic episode (an increase in SBP 30 mmHg or more compared with the presedation reading); two of them showed an elevation of SBP more than 160 mmHg and were treated with hydralazine 5 mg i.v. bolus followed by 10 mg/h i.v. infusion, compared with one patient only in the Mg group (5%) who suffered from a dysreflexic episode (SBP 135 mmHg), with no need for medication.
| Discussion|| |
SCI patients with lesions above T6 are susceptible to develop AD during urological procedures as a result of exaggerated sympathetic excitation . The pathophysiology of AD involves the loss of higher center inhibition of the sympathetic outflow . Patients with chronic SCI are also known to have decreased levels of circulating catecholamines and an increased sensitivity to norepinephrine . In addition, plasma norepinephrine levels rise markedly during episodes of AD . Dexmedetomidine, a highly selective α2-adrenergic agonist, reduces circulating catecholamines and has sedative and analgesic properties . Thus, dexmedetomidine, theoretically, can be used as a safe sedative agent during MAC in patients with chronic SCI.
In our study, dexmedetomidine infusion was not able to provide adequate control of dysreflexic episodes, and 35% of the patients showed elevation of BPs and drop in HRs. Although only two patients needed treatment, an increase in SBP greater than 20–30 mmHg is considered a dysreflexic episode . In addition, the usual resting arterial BP in patients with cervical and high thoracic SCI is ∼15–20 mmHg lower than that in the normal population; thus, the acute elevation of BP to normal or slightly elevated ranges could indicate AD in these patients ,.
On the other hand, dexmedetomidine infusion was capable of controlling the dysreflexic signs and providing hemodynamic stability in a case reported to have an open bladder stone removal . But it should be considered that the patient had a lower level of lesion (T7) and the infusion rate was higher (0.6/kg/h). In addition, dexmedetomidine infusion could control the catecholamine-induced stress response in many different situations. It has been reported that perioperative use of dexmedetomidine provides a steady hemodynamic course and blunts fluctuations at intubation and extubation . In another study, dexmedetomidine administered 15 min before the induction of anesthesia attenuated the hemodynamic responses to laryngoscopy and endotracheal intubation and diminished the isoflurane requirements during the surgery .
Our results showed an elevation in serum adrenaline and noradrenaline during cystoscopy with dexmedetomidine infusion. In a case report for pheochromocytoma resection, researchers found a significant reduction of serum noradrenaline with dexmedetomidine infusion but the serum adrenaline was not affected . Furthermore, Kallio et al.  showed that dexmedetomidine caused a dose-dependent decrease in arterial BP and HR and a decline in the plasma level of norepinephrine. Whereas, in another case report, dexmedetomidine infusion could not provide hemodynamic stability and failed to control the serum norepinephrine level during manipulation of pheochromocytoma tumor .
Our study showed that the addition of single i.v. dose of magnesium sulfate to dexmedetomidine infusion provided higher control for dysreflexic episodes. Only one patient in the Mg group in our study (5%) showed elevation of BP but needed no treatment.
In agreement with that, Maehama et al.  described in a case report the successful use of magnesium sulfate in the management of AD occurring during labor in a patient with high SCI. In addition, magnesium sulfate has been used successfully to control a life-threatening dysreflexic attack in a patient with high SCI in an intensive care setting . Moreover, i.v. magnesium sulfate has proven useful in controlling paroxysmal hypertension associated with tetanus and pheochromocytoma . It has also been shown to attenuate the hemodynamic stress responses to pneumoperitoneum by changing neurohumoral responses .
Our observations revealed that i.v. bolus of magnesium suppressed the release of catecholamine as indicated by the unchanged serum level of catecholamine intaoperatively and postoperatively. James et al.  supported these results: they proved that an i.v. bolus of 60 mg/kg magnesium sulfate was adequate to control the cardiovascular response and inhibit the catecholamine release associated with tracheal intubation. Another study by Jee and colleagues  showed that an i.v. bolus of 50 mg/kg magnesium sulfate was able to suppress the catecholamine release as indicated by the unchanged serum catecholamine level in response to capnoperitoneum.
Magnesium controls catecholamine-induced hypertensive crises through several antiadrenergic mechanisms of which calcium antagonism is of primary importance . Magnesium is an essential regulator of calcium movement in and out of the cell, and of the actions of calcium within the cell . In addition, magnesium competes with calcium for transmembrane channels. By these mechanisms, magnesium inhibits catecholamine release both from the adrenal medulla and from adrenergic nerve endings. Magnesium causes a reduction in systemic vascular resistance by a direct vasodilator effect on vessel walls  and by direct blockade of catecholamine receptors . Moreover, high-dose magnesium attenuates vasopressin-stimulated vasoconstriction and normalizes sensitivity to vasopressin . Moroever, magnesium possesses anti-arrhythmic properties, and offers protection from catecholamine-induced myocarditis by preserving intracellular adenosine triphosphate and glycogen stores and by reducing lactate production ,,,.
The serum magnesium concentration required to exert its catecholamine-suppressive effect and vasodilator effect ranges between 2 and 4 mmol/l ,. Our results showed that a single i.v. dose of 50 mg/kg of magnesium sulfate was enough to raise serum magnesium level up to 2 mmol/l and maintain that level for almost 1 h after the procedure. In agreement with that, it has been found that a magnesium sulfate bolus of 50 mg/kg was enough to increase the serum magnesium level to the above-mentioned range within 10 min after i.v. injection .
| Conclusion|| |
Addition of a single i.v. dose of magnesium sulfate to dexmedetomidine infusion provides a better control of BP and HR, reduces the incidence of autonomic hyperreflexia during cystoscopy, and provides better control for serum catecholamine levels in patients with high level of chronic SCI.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Teasell RW, Arnold JM, Krassioukov A, Delaney GA. Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil 2000; 81:506–516.
Mathias CJ, Frankel HL. Cardiovascular control in spinal man. Annu Rev Physiol 1988; 50:577–592.
Yarkony GM, Katz RT, Wu YC. Seizures secondary to autonomic dysreflexia. Arch Phys Med Rehabil 1986; 67:834–835.
Eltorai I, Kim R, Vulpe M, Kasravi H, Ho W. Fatal cerebral hemorrhage due to autonomic dysreflexia in a tetraplegic patient: case report and review. Paraplegia 1992; 30:355–360.
Valles M, Benito J, Portell E, Vidal J. Cerebral hemorrhage due to autonomic dysreflexia in a spinal cord injury patient. Spinal Cord 2005; 43:738–740.
Dolinak D, Balraj E. Autonomic dysreflexia and sudden death in people with traumatic spinal cord injury. Am J Forensic Med Pathol 2007; 28:95–98.
Krassioukov A, Claydon VE. The clinical problems in cardiovascular control following spinal cord injury: an overview. Prog Brain Res 2006; 152:223–229.
Colachis S. Autonomic hyperreflexia with spinal cord injury. J Am Paraplegia Soc 1992; 15:171–186.
James MFM. Clinical use of magnesium infusions in anaesthesia. Anesth Analg 1992; 74:129–136.
Arcangeli A, D’Aló C, Gaspari R. Dexmedetomidine use in general anaesthesia. Curr Drug Targets 2009; 10:687–695.
Ramsay M, Savege T, Simpson BR, Good R. Controlled sedation with alphaxolone alphadolone. Br Med J 1974; 2:656–659.
Cormier CM, Mukhida K, Walker G, Marsh DR. Development of autonomic dysreflexia after spinal cord injury is associated with a lack of serotonergic axons in the intermedio-lateral cell column. J Neurotrauma 2010; 27:1805–1818.
Hambly PR, Martin B. Anaesthesia for chronic spinal cord lesions. Anaesthesia 1998; 53:273–289.
Claydon VE, Elliott SL, Sheel AW, Krassioukov A. Cardiovascular responses to vibrostimulation for sperm retrieval in men with spinal cord injury. J Spinal Cord Med 2006; 29:207–216.
Lee KH. Dexmedetomidine for chronic spinal cord patients. J Anesth 2014; 28:953.
Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P et al.
The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 2000; 90:834–839.
Aho M, Lehtinen AM, Erkola O, Kallio A, Korttila K. The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy. Anesthesiology 1991; 74:997–1002.
Kallio A, Scheinin M, Koulu M, Ponkilainen R, Ruskoaho H, Viinamäki O et al.
Effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on hemodynamic control mechanisms. Clin Pharmacol Ther 1989; 46:33–42.
Khetarpal M, Yadav M, Kulkarni D, Gopinath R. Role of dexmedetomidine and sevoflurane in the intraoperative management of patient undergoing resection of phaeochromocytoma. Indian J Anaesth 2014; 58:496–497.
Maehama T, Izena H, Kanazawa K. Management of autonomic hyperreflexia with magnesium sulfate during labor in a woman with spinal cord injury. Am J Obstet Gynecol 2000; 183:492–493.
Jones NA, Jones SD. Management of life-threatening autonomic hyperreflexia using magnesium sulphate in a patient with a high spinal cord injury in the intensive care unit. Br J Anaesth 2002; 88:434–438.
James MFM. Use of magnesium sulphate in the anaesthetic management of phaeochromocytoma: a review of 17 anaesthetics. Br J Anaesth 1989; 62:616–623.
Jee D, Lee D, Yun S, Lee C. Magnesium sulphate attenuates arterial pressure increase during laparoscopic cholecystectomy. Br J Anaesth 2009; 103:484–489.
James MF, Beer RE, Esser JD. Intravenous magnesium sulfate inhibits catecholamine release associated with tracheal intubation. Anesth Analg 1989; 68:772–776.
Fawcett. JW, Haxby EJ, Male DA. Magnesium: physiology and pharmacology. Br J Anaesth 1999; 83:302–320.
Altura BM, Altura BT. Magnesium and vascular tone and reactivity. Blood Vessels 1978; 15:5–16.
Laurant P, Touyz RM, Schiffrin EL. Effect of magnesium on vascular tone and reactivity in pressurized mesenteric resistance arteries from spontaneously hypertensive rats. Can J Physiol Pharmacol 1997; 75:293–300.
James MFM, Mason EDM. The use of magnesium sulphate infusions in the management of very severe tetanus. Intensive Care Med 1985; 11:5–12.
O’Riordan JA. Pheochromocytomas and anesthesia. Int Anesthesiol Clin 1997; 35:99–127.
James MF, Cork RC, Dennett JE. Cardiovascular effects of magnesium sulphate in the baboon. Magnesium 1987; 6:314–324.
Pritchard JA, Pritchard SA. Standardized treatment of 154 consecutive cases of eclampsia. Am J Obstet Gynecol 1975; 123:543–552.
[Table 1], [Table 2], [Table 3], [Table 4]