Pseudoseizures and asthma.

BACKGROUND: Sexual abuse and head injury are important risk factors of pseudoseizures, reported in about a third of patients. Clinical experience suggests that asthma is another possible risk factor. OBJECTIVES: To determine the relative prevalence of asthma in patients with pseudoseizures. METHODS: A retrospective record review was undertaken of reported asthma in 102 patients with pseudoseizures and 70 psychotic controls. The pseudoseizure patients were subgrouped according to method of diagnosis: 47 in whom epilepsy was excluded by capturing a typical attack on video-electroencephalographic monitoring (VEEM), and 55 not diagnostically confirmed with VEEM. RESULTS: Asthma was reported in 26.5% of pseudoseizure patients, compared with 8.6% of the psychotic controls (chi(2) = 8.6; p = 0.003). Asthma was reported at similar rates in the VEEM confirmed (29.8%) and non-VEEM confirmed (23.6%) pseudoseizure subgroups. The significant excess of reported asthma held for both the VEEM confirmed subjects (Pearson's chi(2) = 5.4, p = 0.02) and non-VEEM confirmed subjects (Pearson's chi(2) = 8.9, p = 0.003). CONCLUSIONS: There is an association between pseudoseizures and reported asthma. Various models are proposed whereby somatisation, anxiety hyperventilation, and dissociative elaboration may account for the observed association. Both asthma and anxiety hyperventilation may be important risk factors for the development of pseudoseizures. The reported asthma may itself be psychogenic in origin in a proportion of patients. Confirmatory prospective studies are indicated.

Erythropoietin response to hypoxia in patients with diabetic autonomic neuropathy and non-diabetic chronic renal failure.

AIMS: An erythropoietin (EPO)-deficient anaemia is recognized in Type 1 diabetic patients with early nephropathy and symptomatic autonomic neuropathy (DN). The aim of this study was to determine whether the EPO response to hypoxia was deficient in order to clarify the mechanisms involved in this process. METHODS: Five Type 1 diabetic patients DN (age 39 (28-48) years (mean (range))) with EPO-deficient anaemia (haemoglobin, Hb 10.6 (9.5-12.0) g/dl, EPO 5.0 (3.2-6.5) IU/l) and early diabetic nephropathy (persistent proteinuria 1161.6 (130-2835) mg/day, serum creatinine 97.6 (63-123) micromol/l)) were compared with nine normal subjects (age 31 (24-39) years, Hb 13.4 (11.8-15.7) g/dl, EPO 7.6 (5.6-10.3) IU/l) and four patients with non-diabetic advanced chronic renal failure RF (proteinuria 2157.5 (571-4578) mg/day, serum creatinine 490.2 (406-659) micromol/l, Hb 10.3 (9.0-11.3) g/dl, EPO 4.6 (2.9-8.5) IU/l). The subjects were exposed to 6 h of hypoxia (inspired oxygen 11.6-12.6%) by breathing a gas mixture via a hood. Hourly serum EPO levels were measured. RESULTS: All groups showed a rise in EPO production after 2 h. The diabetic DN group achieved a similar maximal response to the normal subjects at 6 h (EPO 17.3 +/-5.4 vs. 17.8 +/-7.9 IU/l). The renal failure patients mounted an EPO response to hypoxia but at lower EPO levels. CONCLUSIONS: Although the DN patients have inappropriately low EPO levels for the severity of their anaemia, they can mount an appropriate EPO response to moderate hypoxia. The mechanism underlying the EPO-deficient anaemia present in some diabetic patients remains unclear.

Hyperventilation and asymptomatic chronic asthma.

BACKGROUND: We have consistently argued that mild asthma is an important underlying aetiological factor in patients with severe symptomatic hyperventilation. While hyperventilation has been demonstrated in acute asthma, there have been few studies in mild chronic asthma, and mechanisms are uncertain. METHODS: Twenty three currently asymptomatic chronically asthmatic patients (occasional use of bronchodilators, normal lung function, hyperresponsive to methacholine) were studied and 17 matched normal subjects acted as controls. Ventilation, pattern of breathing, arterial carbon dioxide and oxygen tensions (PaCO(2), PaO(2)), end tidal PCO(2) (PETCO(2)), standard lung function, airway responsiveness to methacholine, airway inflammation assessed by eosinophils in induced sputum, and psychiatric morbidity (Spielberger STAI-Y and Beck Depression Inventory) were measured. RESULTS: Despite the absence of current asthmatic symptoms, no clinical evidence of hyperventilation, and normal lung function in the patients with asthma, PaCO(2) and PETCO(2) were significantly (p<0.01) lower in the patients than in the control group (mean (SD) PaCO(2) 4.96 (0.43) kPa for patients versus 5.27 (0.38) kPa for controls (mean difference 0.31 kPa, 95% confidence interval (CI) 0.06 to 0.56, p<0.02)). PETCO(2) was very similar to PaCO(2) in both groups (mean (SD) PETCO(2) 4.89 (0.47) kPa for the patients and 5.28 (0.40) for the controls (mean difference 0.39 kPa, 95% CI 0.12 to 0.66, p<0.01)). There was no significant difference in ventilation or respiratory pattern between the two groups. The reduced PaCO(2) in the asthmatic patients correlated significantly with the concentration of methacholine provoking a fall in FEV(1) of more than 20% (PC(20)) (r = 0.56, p<0.01) but not with any aspect of lung function, eosinophil count, or anxiety/depression. CONCLUSION: Mild asymptomatic asthma is not associated with clinically significant hyperventilation but is associated with a significant reduction in both arterial and end tidal PCO(2) which relates to airway hyperresponsiveness rather than to the degree of airway obstruction or mucosal inflammation. Anxiety and depression appear not to be implicated.

Effects of alcohol on respiratory variables in normal humans.

The study is designed to clarify the effect of low doses of alcohol on respiratory variables in air breathing normal subjects. Each subject was given an initial loading dose of alcohol (0.270 g/kg) followed, half an hour later, by a second dose (0.135 g/kg). Blood alcohol increased to a mean value of 52.0 +/- 3.0 (SEM) mg/100 ml at 1 hour. Resting ventilation increased significantly from a mean value of 6.25 +/- 0.41 litres min(-1) to 7.20 +/- 0.31 litres min(-1) 1 hour after alcohol (p= 0.025). Mean inspiratory flow was also increased (p= 0.045). End-tidal PCO² (PET CO²) showed a highly significant fall (1.87 +/- 0.35 mm Hg; p < 0.001) without a significant change in CO2 production rate (p > 0.05). PET CO² variability (100 x SD/mean) was low (mean 2.4%) and unaffected by alcohol. The longest end-expiratory pauses (apnoeas) observed for each subject were shortened significantly by alcohol (1.030 +/- 0.194 s and 0.690 +/- 0.138 s; p = 0.01). Moderate doses of alcohol in normal subjects, therefore lower PET CO² and shorten end-expiratory pauses (apnoeic periods) but do not affect PET CO² variability.

Effects of oral ethanol on end-tidal CO2tension in patients misusing alcohol.

This study examines the effect of oral ethanol ingestion on P(et)CO2 and other respiratory variables in alcohol-misusing subjects. Twelve patients were given a loading dose of alcohol (0.270 g/kg) followed by a second dose (0.135 g/kg) half an hour later, increasing blood alcohol to a mean of 82.0 +/- 10.3 (SEM) mg/100 ml at 1 hour. Five patients were classified as hazardous drinkers with evidence of mild alcohol dependence but no toxicity (Severity of Alcohol Dependency (SADQ) score < 15/60; serum carbohydrate-deficient transferrin < 6%). These patients showed a significant fall in mean end-tidal PCO² (P(et)CO2) on alcohol (2.08 +/- 0.61 mm Hg; p = 0.027) with slightly increased ventilation (1.76 +/- 0.94 1 min(-1), p = 0.14); responses similar to those previously reported for normal subjects. Seven patients had evidence of moderate alcohol dependency and/or recent use (SADQ > 15/60; CDT > 6%). In these patients P et CO2 did not fall after alcohol challenge (mean change + 0.61 mm Hg; p > 0.30). There were significant correlations between the changes in P et CO2 and CDT (n = 12; r(s)= 0.66, p = 0.019) and SADQ (n = 11; r(s)= 0.688, p = 0.019). The results show that P(et)CO2 control is abnormal in the alcohol dependency syndrome.

Severe hyponatraemia secondary to beer potomania complicated by central pontine myelinolysis.

A case of severe hyponatraemia in a 56-year-old male alcohol misuser secondary to beer potomania is presented. In view of severe volume depletion and the patient's inability to drink, normal saline was cautiously infused. Despite initial improvement, he subsequently deteriorated neurologically. Magnetic resonance imaging demonstrated the classical lesion of central pontine myelinolysis (CPM). The rate of correction of plasma sodium was within limits normally considered safe. Beer potomania should be considered as a cause of hyponatraemia in alcohol misusers. Recognition is important as the electrolyte imbalance repairs simply with cessation of alcohol intake and institution of normal diet. Correction of chronic hyponatraemia by infusion of normal or hypertonic saline should not be attempted unless life-threatening neurological complications supervene. When the balance of risks favours correction, caution should be exercised, as CPM may occur. Although a rate of correction of plasma sodium of up to 10 mM per 24-hour period has been associated with a low risk of precipitating CPM, this case illustrates that a completely safe rate of correction probably cannot be defined.

Control of the respiratory cycle in conscious humans.

We studied in conscious humans the relative strength of mechanisms controlling timing and drive components of the respiratory cycle around their resting set points. A system of auditory feedback with end-tidal PCO2 held constant in mild hyperoxia via an open circuit was used to induce subjects independently to change inspiratory time (TI) and tidal volume (VTI) over a wide range above and below the resting values for every breath for up to 1 h. Four protocols were studied in various levels of hypercapnia (1-5% inspired CO2). We found that TI (and expiratory time) could be changed over a wide range (1.17 - 2.86 s, P < 0.01 for TI) and VTI increased by > or = 500 ml (P < 0.01) without difficulty. However, in no protocol was it possible to decrease VTI below the free-breathing resting value in response to reduction of auditory feedback thresholds by up to 600 ml. This applied at all levels of chemical drive studied, with resting VTI values varying from 1.06 to 1.74 liters. When reduction in VTI was forced by the more "programmed" procedure of isocapnic panting, end-expiratory of volume was sacrificed to ensure that peak tidal volume reached a fixed absolute lung volume. These results suggest that the imperative for control of resting breathing is to prevent reduction of VTI below the level dictated by the prevailing chemical drive, presumably to sustain metabolic requirements of the body, whereas respiratory timing is weakly controlled consistent with the needs for speech and other nonmetabolic functions of breathing.

Patients with acute hyperventilation presenting to an inner-city emergency department.

We studied 23 consecutive patients with acute hyperventilation presenting to an inner-city emergency department, diagnosed on clinical grounds by the attending physician and confirmed by arterial blood gas values in 5 patients. An organic basis for the presenting complaints was excluded and chest radiograph, serum biochemistry, blood cell count, and thyroid function test results were normal. The male to female ratio was 12:11. Presenting complaints were dyspnea (61%), paresthesia (35%), chest pain or tightness (43%), muscle spasm (9%), dizziness (13%), palpitations (13%), and panic (30%). Similar previous episodes were reported in 74%. Misattribution of the presenting complaints to a cardiac or other life-threatening disorder was reported in 20 patients (87%) and was the main reason for their presentation to the hospital. Although no patients presented with clinical features of asthma, 7 (30%) were known asthmatics receiving treatment and another 10 (44%) had a history and investigation results suggestive of asthma. Only 2 had a history of anxiety or depression, but 17 (78%) patients exceeded the threshold for anxiety or panic on Clinical Interview Schedule (CIS-R) interview (score > or = 12). Marihuana or alcohol abuse were involved in 17% with a history of past abuse in 26%. When assessed 2 months after the attack, 13 (57%) had resting or stressor-induced hyperventilation with a significant (p < 0.05) association with asthma but not with a positive CIS-R score. These results illustrate the multifactorial basis of acute hyperventilation, the importance of misattribution, and the danger of using the term "hyperventilation syndrome" in the emergency department.

Control of expiratory time in conscious humans.

Combinations of 17 normal awake humans breathed mildly hyperoxic and hypercapnic gas mixtures via a pneumotachograph into an open circuit. Respiratory pattern was measured for each breath in real time by computer. Use of computer-controlled auditory feedback at a constant end-tidal PCO2 (PETCO2) allowed prolonged changes of 1) inspiratory time (TI) at constant inspired tidal volume (VTI), 2) VTI up and down in repeated steps at constant TI, and 3) expiratory time (TE) at constant VTI. The remaining variables were free to be determined by the subjects' automatic respiratory control mechanisms. We showed that TE changed in parallel with the change in TI despite constant VTI, TE did not change in response to step changes in VTI at constant TI, and large changes in TE had no influence on the subsequent TI, but VTI increased slightly as TE lengthened despite clamping. Time for expiratory flow (TE--end-expiratory pause) changed in parallel with TE in all protocols. Thus, in conscious humans, inspiratory timing has a direct influence on expiratory timing, independent of volume change and chemical drive, but expiratory timing has no influence on the inspiratory timing of the subsequent breath but has a small influence on volume.

Post-hyperventilation apnoea in conscious humans.

1. In nine normal subjects, analysis was performed of the number, length and location of apnoeic pauses during 20 min of recovery following voluntary overbreathing (VHV). Four different rates of recovery of end-tidal PCO2 (PET,CO2), studied in randomized order, were induced by overbreathing to 15 or 25 mmHg, each for 3 or 6 min. Subjects breathed mildly hyperoxic gas mixtures (inspired PO2 approximately 250 mmHg) to and fro into an open circuit via a mouthpiece and pneumotachograph. 2. Apnoeic pauses rarely occurred immediately after the end of VHV but gradually increased in number and length. When averaged across all subjects and protocols, the largest pauses occurred 2.0 +/- 0.3 min (S.D.; range 1.6-2.4 min) after the end of VHV. Based on a definition of apnoea as expiratory time greater than 6 s, apnoeas occurred between mean times of 0.8 and 5.6 min after the end of VHV, the end of this period being associated with a mean PET,CO2 value of 36.4 mmHg, which was below the initial mean resting value of 39.8 mmHg. 3. Within this apnoeic period, 80% of experiments produced apnoeas of less than 10 s duration, 61% of between 10 and 20 s duration and 42% of between 20 and 30 s duration. Only one out of nine subjects consistently failed to show apnoeas. 4. The range of lengths of individual apnoeas and the number per minute were independent of the length and level of VHV and were not significantly different between the four protocols. 5. The number and length of apnoeas did not change in repeated runs in each subject. We were not able to confirm previous reports that apnoeas occurred more frequently in subjects familiar with the experiment. 6. These results reconciled previous studies showing either apnoea or hyperpnoea following voluntary overbreathing in conscious humans. They showed an initial period of heightened breathing lasting about a minute with few apnoeas, consistent with 'after-discharge'. Beyond that, apnoeas occurred as an 'all-or-nothing' phenomenon as long as PET,CO2 was on average less than 3.4 mmHg below resting PET,CO2. The occurrence and length of apnoeas was consistent in individual subjects with no evidence of a learning effect.

Hyperventilation and chronic fatigue syndrome.

We studied the link between chronic fatigue syndrome (CFS) and hyperventilation in 31 consecutive attenders at a chronic fatigue clinic (19 females, 12 males) who fulfilled criteria for CFS based on both Oxford and Joint CDC/NIH criteria. All experienced profound fatigue and fatigability associated with minimal exertion, in 66% developing after an infective episode. Alternative causes of fatigue were excluded. Hyperventilation was studied during a 43-min protocol in which end-tidal PCO2 (PETCO2) was measured non-invasively by capnograph or mass spectrometer via a fine catheter taped in a nostril at rest, during and after exercise (10-50 W) and for 10 min during recovery from voluntary overbreathing to approximately 2.7 kPa (20 mmHg). PETCO2 < 4 kPa (30 mmHg) at rest, during or after exercise, or at 5 min after the end of voluntary overbreathing, suggested either hyperventilation or a tendency to hyperventilate. Most patients were able voluntarily to overbreathe, but not all were able to exercise. Twenty-two patients (71%) had no evidence of hyperventilation during any aspect of the test. Only four patients had unequivocal hyperventilation, in one associated with asthma and in three with panic. Only one patient with severe functional disability and agoraphobia had hyperventilation with no other obvious cause. A further five patients had borderline hyperventilation, in which PETCO2 was < 4 kPa (30 mmHg) for no more than 2 min, when we would have expected it to be normal. There was no association between level of functional impairment and degree of hyperventilation. There is only a weak association between hyperventilation and chronic fatigue syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of hypocapnic symptoms to rate of fall of end-tidal PCO2 in normal subjects.

Hyperventilation is of little clinical relevance unless it causes symptoms. These are often non-specific. Their threshold for onset and relation to steady level of arterial (or its equivalent, end-tidal PCO2; PETCO2) are uncertain, and it has been suggested that they may relate better to the rate of fall of PCO2 than to the absolute level. We investigated this in nine normal subjects, who breathed to and fro through a pneumotachograph into an open circuit in which the concentration of CO2 could be varied. Tidal volume, respiratory frequency and ventilation was measured on-line by a Compaq computer, and PETCO2 at the mouth was measured by capnograph. Subjects overbreathed at a fixed rate and depth until symptoms consisting of dizziness, paraesthesiae and light headedness occurred. Then, without their knowledge and while they continued to overbreathe, inspired CO2 was increased to restore PETCO2 to normal and abolish symptoms, and was then withdrawn again over either approximately 0.1, 2.5 or 5 min until symptoms were again reported. The PETCO2 at this point was noted. The three protocols were performed in each subject in a random order and the same symptoms were reported each time. When averaged across all subjects, symptoms occurred at mean PETCO2 values of 20.3, 19.2 and 18.6 mmHg (2.71, 2.56 and 2.48 kPa), respectively. These were not significantly different, and it can be concluded that there was no influence of rate of fall of PCO2 on threshold for symptoms. Chest pain only occurred in one subject and may have a different mechanism.

Hyperventilation provocation in patients with chest pain and a negative treadmill exercise test.

Seventeen (39%) of 44 patients with chest pain but without significant ST depression on treadmill exercise had their usual chest pain reproduced during or after 3 min of voluntary hyperventilation (VHV) at rest. These patients with hyperventilation positive tests had not only significantly more hyperventilation-related symptoms and respiratory complaints but also shorter breath-holding times, lower mean resting end-tidal pCO2 and higher mean respiratory rates than those with negative tests and normal controls. Of the psychological variables, only phobic avoidance scores for agoraphobia were higher in patients with positive tests. These findings suggest that in two fifths of patients with exercise tests negative for ischaemia, chest pain is associated with HV, but abnormalities of breath control and relative hypocapnia are present even in the absence of chest pain. It is possible that a chronic abnormality of respiratory control may interact with attitudinal factors in the experience of non-cardiac chest pain.