Abstract
Dialysis may induce severe headache as a result of a large amount of water and electrolyte shifts. It is important to recognize it because it can be a great problem to the patient and changing dialysis parameters or methods can prevent it. In this study we investigated the frequency and clinical characteristics of headaches occurring during haemodialysis (HD). Thirty female and 33 male patients with chronic renal failure on regular dialysis for at least 6 months in the HD unit of the Internal Medicine Department from 1996 to 2000 participated in the study. The dialysis solution contained acetate in 35 patients and bicarbonate in 28 patients. In all patients capillary dialysers and Cuprophan membranes were used and every session of dialysis lasted 4 h. All patients received the same questionnaire and they were visited randomly. Dialysis headache (DH) diagnosis was made according to the criteria of the International Headache Society. Patients with primary headache and under drug treatment during HD, which can cause headache, were excluded from the study. The frequency of DH, its relation to gender, age, dialysis technique and parameters and its features were investigated. DH was detected in 48% (n = 30) of the study group. Compared with dialysis solutions, no difference was found between patients with and without DH. The difference in the pre- and post-dialysis value of urea in patients with DH was statistically significant (P < 0.05). Patients with DH showed significantly higher mean systolic and diastolic blood pressure predialysis values in comparison with patients without DH (systolic, P < 0.001; diastolic, P < 0.01), whereas post-treatment values did not differ between the two groups. Fronto-temporal location, moderate severity, throbbing quality and short duration (<4 h) were the most prevalent features of DH in patients.
Introduction
Haemodialysis (HD) prolongs the life expectancy of patients suffering from terminal-stage renal insufficiency. Development or progress of complications such as encephalopathy and neuropathy due to uraemia can be prevented by haemodialysis, but this treatment modality itself brings about acute (agitation, delirium, muscle cramps, convulsions, headache, irritability, etc.) or long-term complications (Wernicke's encephalopathy, dementia, amyloid neuropathy due to amyloid deposition, etc.) (1).
Although headache is one of the most frequently encountered neurological symptoms during HD, studies reporting its features are limited.
Bana et al. first described headache during HD in 1972 and its frequency was reported to be 70% (2). It was suggested that the large amount of water and electrolyte shifts during dialysis could produce headache. The exact description of HD-related headache was given by the International Headache Society (IHS) in 1988 (3). According to IHS criteria dialysis headache (DH) was defined as the headache with onset during HD, which terminates within 24 h after dialysis, occurs during at least half of haemodialyses and at least three times, and can be prevented by changing dialysis parameters. These criteria were revised in 2003 (4, 5).
In this study the frequency and clinical features of DH were examined and the type of the dialysis and its parameters were compared among patients with and without headache.
Methods
Thirty female and 33 male patients with chronic renal failure on regular dialysis for at least 6 months in the HD unit of the Internal Medicine Department from 1996 to 2000 participated in the study. The dialysis solution contained acetate in 35 patients (group I) and bicarbonate in 28 patients (group II). In all patients capillary dialysers and Cuprophan membranes were used and every session of dialysis lasted 4 h. All patients received the same questionnaire and they were visited randomly. DH diagnosis was made according to the criteria of the IHS, 1988. All patients also fulfilled the revised IHS criteria of 2003. Patients under medications which might cause headache and having any type of primary headache unrelated to HD were excluded. All patients were visited by neurologists and received a standard questionnaire examining the frequency, location, intensity, quality and duration of DH besides their demographic data. The intensity of the headache was rated as mild, moderate, severe or very severe. Patients reporting DH were further compared with the group of patients without DH according to dialysis technique, arterial blood pressure, and pre- and post-treatment values of blood parameters such as urea, Na+, K+ and creatinine. χ2 analysis of variance (ANOVA) and Mann–Whitney U-test were used to examine association between categorical and continuous variables. Alpha was set at 0.05 to determine statistical significance.
Results
Forty-eight percent of patients reported DH. Table 1 shows demographic and clinical characteristics of the study population. DH was more frequent in women than in men. The frequency of DH showed no significant difference between groups (group I 46%, group II 50%). Table 2 show pre- and post-dialysis blood values of urea, Na+, K+ and creatinine in patients with and without DH. The difference between pre- and post-dialysis values of urea in patients with DH was statistically significant (P < 0.05). Table 3 show pre- and post-dialysis mean systolic and diastolic blood pressure values in patients with and without DH. Patients with DH showed significantly higher mean systolic and diastolic blood pressure predialysis values in comparison with patients without DH (systolic, P < 0.001; diastolic, P < 0.01), whereas post-treatment values did not differ between the two groups.
Demographic and clinical characteristics of the study population
DH, Dialysis headache; HD, haemodialysis; SD, standard deviation.
The difference in pre- and post-treatment values of urea, Na+, K+ and creatinine in patients
DH, Dialysis headache.
Pre-and post-dialysis values of systolic and diastolic blood pressure in patients
DH, Dialysis headache.
The location of pain was fronto-temporal in 50% (n = 15), occipital in 27% (n = 8), and diffuse in 23% (n = 7) of patients. Eighty-seven percent of patients (n = 26) reported the quality of their headaches as being throbbing, whereas four patients (13%, n = 4) had headaches with dull character. The intensity of the headache was moderate in 73% (n = 22), and severe in 27% (n = 8) of patients. The duration of the headache was reported to be < 4 h in 63% (n = 19), and between 4 and 24 h in 37% (n = 11) of patients. Table 4 show the features of DH in our patient groups.
Features of the dialysis headache
Discussion
Headache is common in patients receiving dialysis treatment. There are few studies in the literature investigating the clinical features of DH (2, 6). Although the frequency of headache occurring in HD patients in the first study is reported to be 70%, this rate decreases to 18.1% if 44 included patients are further subdivided as having migrainous headache, tension-type headache, headache associated with onset of renal disease and dialysis headache according to the IHS criteria (2). Antoniazzi et al. reported that 50 (57.5%) of 123 patients experienced headache during an HD session. Of those, 34 (27.6%) were classified as DH (6). In our study this frequency is 48%, which is significantly higher than in previous reports. The features of the headache described by Bana et al. were similar to those found in our study, being temporally directly related to the HD, which frequently began after some hours of therapy, beginning with moderate intensity but becoming severe, located bifrontally and having a throbbing character.
There are several factors which seem to be directly responsible for DH, and which also constitute the parameters of our study. Among these factors, which are related to the patient, are those of paramount importance as risk factors for DH. DH occurred more frequently among women than men (60% vs. 36%), similar to other well-known types of headaches such as migraine or tension-type headache (7). Another factor is an experience of a primary headache in the predialysis period, especially of a migrainous or a tension type. To prevent a misdiagnosis of DH in patients with a primary headache we excluded these patients from the study.
The type of dialyser is another factor related to DH. To evaluate this, we divided our patients according to their dialysate composition, receiving either acetate or bicarbonate dialysis. The frequency of headache did not differ among these subgroups of patients. Bana et al. found a frequency of headache of 77% among patients using kiil dialyser and 46% using kolff dialyser (2). This significant difference was related to the more frequent experience of headache during the predialysis period in the first group of patients, but not to the type of dialyser itself. Although this result was concordant with ours, another study from Neyer et al. (8) reported that the headache during the procedure was more frequent and severe in patients receiving acetate dialysis (AD) than in those receiving bicarbonate dialysis (BD), and the EEG changes following the treatment procedures were reported also to be more frequently encountered in patients undergoing AD. The authors explained this difference based on corrected metabolic acidosis; after AD there was a negative base excess and a fall in PaCO2, whereas after BD the PaCO2 increased the base balance, resulting in a positive shifting. After AD due to decreased cerebral blood circulation there was a concomitant cerebral dysfunction (8). Although this hypothesis seems to be relevant, our results do not support it.
Another factor which may play a role in the development of DH is biochemical changes during HD. The abrupt decrease in blood level of urea during HD does not cause a similar concomitant decrease in the brain due to the blood–brain barrier. An osmotic gradient develops and water shifts into the brain, which results in an increased intracranial pressure and brain oedema. This process is called ‘reverse urea effect’. In experimental models it was shown that urea is not the only element causing an osmotic gradient between the brain and blood, but there are several other unidentified variables called ‘idiogenic osmoles’ capable of a water shift into the brain (1, 9). Bana et al. suggested that a prolonged interval between the dialyses may cause a more prominent difference between the levels of urea in the blood and in the brain after dialysis, which may cause more water shift, and headache (2). In our study the difference in blood urea level pre- and post-treatments was significantly higher in patients with headache than in those without. Other biochemical parameters such as Na, K and creatinine did not differ. Arieff et al. compared slow and fast HD procedures in dogs undergoing experimental kidney insufficiency (1). After rapid dialysis, the cerebral water content and number of osmotically active particles were greater than after slow treatment. Rapid treatment was also associated with the development of measurable blood–brain osmotic gradients and acidosis of the CSF. Osmotic gradient results in the obligatory retention of water by the brain, relative to blood, and leads to cerebral swelling and symptoms such as headache (1, 2, 9). In our patients the intervals between the dialysis procedures and dialysis durations were the same.
Hypertension causing or complicating renal dysfunction is a rare aetiological entity for headache. Hypertension and headache may occur coincidentally together in the same patient, or tension-type headache may develop as a result of anxiety related to hypertension. Other possible causes of headache associated with severe hypertension were detailed in IHS criteria (3, 4). Also, some anti-hypertensive agents such as Ca2+ antagonists and hydralazine may cause hypotension by dilatating cerebral resistance vessels and increasing intracranial pressure (10). In our study the systolic and diastolic blood pressure of patients with DH in the predialysis period was significantly higher than in those patients without DH. The blood pressure measures of both groups of patients did not differ after dialysis. None of our patients’ headache characteristics met the IHS criteria for coexistence of arterial hypertension and headache. We also excluded patients whose headache developed following anti-hypertensive drug use and patients with primary headaches, i.e. patients reporting DH should have another explanation for their headaches than increased blood pressure. Wollf et al. observed hypertensive patients with vascular headache and concluded that headache develops only when the blood pressure decreases from very high to low levels, and does not coexist with increased blood pressure (2). Based on this observation, we also suggest that in patients with DH headache is not related to the increased systolic and diastolic blood pressure during the predialysis period, but to the more pronounced decrease in blood pressure compared with patients without DH after treatment. This decrease may act as a trigger, similar to the mechanism of some anti-hypertensive drugs developing headache dilatation of cerebral blood vessels and inducing headache.
We conclude that HD-related headache is a prevalent type of headache among patients undergoing HD, with female preponderance, beginning after some hours of therapy, having an increasing intensity and a throbbing character which seems to be unrelated to a coexisting primary headache and the type of dialyser, but to be related to the difference of pre- and post-treatment levels of blood urea and blood pressure.