Objectives: Brain death is defined as the permanent absence of all cortical and brain stem reflexes. A wide range of spontaneous or reflex movements that are considered medullary reflexes are observed in heart beating cases that appear brain dead, which may create uncertainty about the diagnosis of brain death and cause delays in deceased-donor organ donation process. We determined the frequency and type of medullary reflexes and factors affecting their occurrence in brain dead cases.

Materials and Methods: During 1 year, 122 cases who fulfilled the criteria for brain death were admitted to the special intensive care unit for organ procurement of Masih Daneshvari Hospital. Presence of spinal reflexes was evaluated by trained coordinators and was recorded in a form in addition to other information including demographic characteristics, cause of brain death, time from detection of brain death, history of craniotomy, vital signs, serum electrolyte levels, and parameters of arterial blood gas determination.

Results: Most cases (63%) included in this study were male, and mean age was 33 ± 15 y. There was ≥ 1 spinal reflex observed in 40 cases (33%). The most frequent reflex was plantar response (17%) following by myoclonus (10%), triple flexion reflex (9%), pronator extension reflex (8%), and undulating toe reflex (7%). Mean systolic blood pressure was significantly higher in cases who exhibited medullary reflexes than other cases (126 ± 19 mm Hg vs 116 ± 17 mm Hg; P = .007).

Conclusions: Spinal reflexes occur frequently in brain dead cases, especially when they become hemo-dynamically stable after treatment in the organ procurement unit. Observing these movements by caregivers and family members has a negative effect on obtaining family consent and organ donation. Increasing awareness about spinal reflexes is necessary to avoid suspicion about the brain death diagnosis and delays in organ donation.

Key words : Medullary reflexes, Brain death, Deceased-donor organ donation

Introduction

Diagnosis of brain death occurs when a set of criteria is observed in a patient, including unresponsiveness, loss of all brain stem reflexes, and apnea, in the absence of confounding factors that may mimic this state.¹ After the first formal definition of brain death in 1968, the diagnosis was disproved by any spon-taneous or reflex movements.² However, since 1981, confirmation of brain death diagnosis has been allowed despite the presence of spinal reflexes, which have been explained as spontaneous or reflex motor activities originating from neurons of the spinal cord in a brain dead body.^3,4

A wide diversity of phenomenology for spinal reflexes associated with brain death has been noted in the literature,^5-7 and the frequency of these move-ments has been reported from 30% to 75% in different studies.^4,8 Observing these movements may create uncertainty about the diagnosis of brain death for health care providers and brain dead next of kin, and may cause delays and failure in deceased-donor organ donation. Therefore, awareness of such reflexes in brain dead cases is important in the process of procuring organs for the increasing number of cases on transplant waiting lists.

The aim of this study was to determine the frequency of various types of medullary reflexes in confirmed brain dead cases and evaluate the effect of different factors on the occurrence of these reflexes.

Materials and Methods

Cases
This cross sectional observational study was performed at the organ procurement unit of Masih Daneshvari Hospital during 1 year beginning June 2011. Within this period, all 122 brain dead cases transferred to this department for organ donation were included. Diagnosis of brain death was confirmed according to the Iran national protocol including the following criteria: (1) deep irreversible coma with a clear cause and the absence of hypo-thermia, administration of sedative or neuro-muscular blocking agents, and metabolic or endocrine disorders resulting in coma; (2) absence of brain stem reflexes; (3) positive apnea test; (4) at least 2 isoelectric electroencephalograms; and (5) definite confirmation of brain death by a medical committee including a neurologist, a neurosurgeon, an internist, and an anesthesiologist. The study was approved by the ethical committee of National Research Institute of Tuberculosis and Lung Diseases, and all of the protocols confirmed to the ethical guidelines of the 1975 Helsinki Declaration.

Evaluation
Demographic characteristics, cause of brain death, time from detection of brain death (d), and history of craniotomy were recorded in a questionnaire for each patient. At 3 hours after admission of each enrolled patient to our intensive care unit, the cases were examined by a trained organ donor coordinator for the presence of any spinal reflexes including Lazarus sign, facial myokymia, myoclonus, opisthotonus, quadriceps contraction, triple flexion reflex, fasciculation, plantar response, pronator extension reflex, undulating toe, respiratorylike movements, hugginglike motion, head turning, limb elevation with neck flexion, tonic neck reflex, and abdominal reflex, and the results were recorded (Table 1).^6,7 Additional data recorded included infusion of inotropic drugs (dopamine, epinephrine, and norepinephrine), blood pressure, heart rate, temperature, serum electrolyte levels (sodium, potassium, magnesium, and calcium), and results of arterial blood gases determination.

Statistical analyses
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 16.0, IBM Corporation, Armonk, NY, USA). Variables were described as mean ± standard deviation (SD) for quantitative variables and number (%) for qualitative variables. Independent sample t test, chi-square test, and Fisher exact test were used for evaluation of associations between the presence of spinal reflexes and different factors. Values of P ≤ .05 were considered significant.

Results

In the 122 brain dead cases enrolled in this study,77 cases (63%) were male. Age of the cases ranged from 4 to 62 years (mean age, 33 ± 15 y). The most common cause of brain death was head trauma (54 cases [44%]). Other causes of death were intra­cerebral hemorrhage in 23 cases (19%), ischemic stroke in 15 cases (12%), hypoxia in 11 cases (9%), postcardio-pulmonary resuscitation in 7 cases (6%), brain tumor in 7 cases (6%), seizure in 3 cases (3%), and drug intoxication in 2 cases (1%).

There were 37 cases (31%) who had undergone craniotomy before the clinical diagnosis of brain death. The time from detection of brain death to patient evaluation at our intensive care unit was 1 to 12 days (mean, 2.6 d).

Mean vital sign measurements at the time of examination for spinal reflexes were 120 ± 17 mm Hg for systolic blood pressure, 76 ± 15 mm Hg for diastolic blood pressure, 92 ± 19 beats per minute for heart rate, and 36.5°C ± 0.7°C for temperature. Regarding inotrope agents, 82 cases (67%) received dopamine infusion, 9 cases (7%) received epinephrine, and 6 cases (5%) received norepinephrine.

Mean serum electrolyte and arterial blood gas parameters were sodium, 147 ± 16 mEq/L; potassium, 4.1 ± 0.7 mEq/L; magnesium, 2 ± 0.6 mEq/L; calcium, 8.3 ± 1.4 mg/dL; pH, 7.34 ± 0.1; pressure of carbon dioxide, 34.4 ± 9.3 mm Hg; pressure of oxygen, 148.9 ± 70.4 mm Hg; and bicarbonate, 18.7 ± 4.3 mEq/L.

There were 40 cases (33%) who had ≥ 1 spinal reflex, with 1 type of reflex in 17 cases (14%), 2 types of movements in 12 cases (10%); and ≥ 3 types of movements in 11 cases (9%). The most frequent reflexes were plantar response (17% of all cases) and myoclonus (10%) (Table 1).

Comparison of variables between cases with and without spinal reflexes showed that mean systolic and diastolic blood pressure were significantly higher in cases who exhibited medullary reflexes than other cases (systolic blood pressure: with reflex, 126 ± 19 mm Hg; without reflex, 116 ± 17 mm Hg; P = .007; diastolic blood pressure: with reflex, 82 ± 18 mm Hg; without reflex, 73 ± 13 mm Hg; P = .003), and there was no other significant differences between the 2 groups (Table 2).

Discussion

This study showed that one-third of the cases who had confirmed diagnosis of brain death exhibited at least 1 type of spinal reflex. Plantar response was the most common movement, and myoclonus and triple flexion reflex were observed with similar frequency as the second most common movement. Significantly higher levels of blood pressure were observed in cases with spinal reflex than other cases.

A wide range of frequencies for spinal reflexes associated with brain death have been reported in different studies. To date, the lowest frequency of these movements was 13.4% in 134 brain dead bodies reported by Döþemeci and coworkers.⁴ In 1973, Jorgensen reported spinal reflexes in 50 of 63 cases (79%), which is the highest rate reported,⁹ and results in the study by Ivan in the same year were similar.⁸ The closest frequency rate to our result was 44% which was reported by Saposnik and associates.¹⁰ It appears that the variety of these rates may be due to different definitions of spinal reflexes in various regions and periods. Some movements that were observed for the first time in a brain dead patient have been assessed carefully and subsequently have been recognized as medullary reflexes. In addition, some spontaneous movements might happen without any stimulation and can be missed by examiners.

The most frequent types of reflexes were plantar response, myoclonus, and triple flexion reflex in this study. Ivan also reported plantar flexion response as the most common reflex, and abdominal reflexes were the second most common reflex.⁸ Triple flexion response was the most frequent and the second most frequent movement in studies by Jorgensen⁹ and Saposnik and coworkers.¹⁰ In the latter study, undulating toe flexion was observed more than other movements. Finger and toe jerk were the most com-mon reflexes reported by Döþemeci and associates.⁴

Although several mechanisms have been sug-gested for the occurrence of spinal reflexes in brain death, the exact pathophysiology is unknown. Proposed mechanisms include hypoxia of spinal neurons isolated from rostral brain areas, elimination of supraspinal inhibitory function on the spinal neuronal networks known as central generators, and muscle denervation, which can explain some move-ments such as facial myokymia in brain death.^6,7,11

To our knowledge, comparison of different characteristics between brain dead bodies with and without reflexes has been presented in only 1 previous study by Saposnik and colleagues in 2005,¹⁰ and the results of our study were similar to that study because mean blood pressure was significantly greater in cases with movements in both studies. In the previous study, similar to our study, there was no significant difference in any other factors such as age, sex, laboratory tests, and vital signs between brain dead cases with and without reflexes.¹⁰

A limitation of the present study was that only brain dead cases with family consent for organ donation were evaluated, and the results may not be generalized to other cases with brain death. However, the fact that the occurrence of spinal reflexes is not rare in brain dead cases was confirmed in this study and previous reports.

In the organ procurement unit, these cases are observed meticulously and treated to maintain organs in a suitable condition for transplant. Therefore, their hemodynamic status remains more stable than before transfer to this unit. These cases have lower levels of blood pressure before transfer to this unit for organ donation. According to our results, greater levels of blood pressure were observed in cases with spinal reflexes, and brain dead cases may be more likely to show movements during treatment in the organ procurement unit with hemodynamic stability.

The effect of observing these movements by either family members or medical staff on the organ donation process is important because it may raise a question about the correctness of the diagnosis of brain death among caregivers, physicians, and specialists who are liable for confirming the diagnosis, and may cause hope among relatives for recovery and result in family refusal for organ donation. Therefore, increasing awareness about the frequency of brain death associated medullary reflexes among the medical team and family members of brain dead cases, especially on the basis of documented research, is important to reduce uncertainty about the diagnosis of brain death and make it easier to decide for organ donation and save other cases.

In conclusion, this study demonstrated that spinal reflexes, especially plantar response, myoclonus, and triple flexion reflex, occur frequently in brain dead cases. These reflexes are more likely to occur when heart beating cases become hemodynamically stable after treatment in the organ procurement unit. Observation of these movements by medical personnel and relatives has a negative effect on obtaining family consent for organ donation. Therefore, informing heath care professionals and family members of brain dead cases about spinal reflexes is necessary to avoid suspicion about the correctness of the brain death diagnosis and delay in organ donation.

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