Hyperventilation and Seizures: Not a New Sense: A Literature Review.

Hyperventilation and seizures have a long association in the clinical literature and were known to have a relationship long before the electroencephalogram (EEG) was used to record changes in brain activity. As the use of EEG recording progressed, hyperventilation was the first activation method used to assist with diagnosis of epilepsy. Along with slowing of brain activity, hyperventilation can activate epileptiform spiking activity in patients with epilepsy. Currently, hyperventilation is used in standard practice to assist with the diagnosis of epilepsy during EEG recording. Hyperventilation activates epileptiform spiking activity more often than seizures but can trigger clinical seizures in up to 50% of patients with generalized epilepsy. It is more likely to trigger events in children with absence seizures than adults, and it acts as a trigger in patients with focal epilepsy far less often. However, while some clinicians suggest that its diagnostic value is limited, especially in adults with focal epilepsies, others suggest that it is simple, safe, and an important diagnostic tool, even in these patients. This review presents the history of hyperventilation and seizures, its use in the clinical practice, and possible mechanisms involved.

Effect of intraoperative mild hyperventilation on the incidence of shoulder pain after laparoscopic sleeve gastrectomy: A randomized, controlled trial.

BACKGROUNDS: To observe the effect of using mild intraoperative hyperventilation on the incidence of postlaparoscopic shoulder pain (PLSP) in patients undergoing laparoscopic sleeve gastrectomy. METHODS: Eighty patients undergoing laparoscopic sleeve gastrectomy, aged 22 to 36 years, with American Society of Anesthesiologists grade I or II, were divided into 2 groups according to method of random number table. A mild hyperventilation was used in group A with controlling pressure of end-tidal carbon dioxide (PETCO2) of 30 to 33 mm Hg, while conventional ventilation was used in group B with PETCO2 35 to 40 mm Hg during the operation. The incidence and severity of PLSP, dosage of remedial analgesia and adverse reactions such as nausea and vomiting at 12, 24, 48, 72 hours and 1 week after surgery were recorded. Arterial blood gas was recorded before anesthesia induction, 20 minutes after pneumoperitoneum, during suture skin, and 24 hours after surgery. RESULTS: Compared with 12, 24, 48, and 72 hours after operation, the incidence of PLSP at 1 week decreased significantly (P < .01). Compared with group B, the incidence of PLSP, pain score, and dosage of remedial analgesic at 12, 24,48, 72 hours, and 1 week after surgery were significantly decreased (P < .01). There was no significant difference between the 2 groups in arterial blood gas analysis before anesthesia induction, 20 minutes after pneumoperitoneum, during suture skin, and 24 hours after surgery (P > .05). There were no significant difference of the occurrence of adverse reactions such as nausea and vomiting between the 2 groups within 1 week after surgery (P > .05). CONCLUSION: Mild hyperventilation can reduce the incidence and severity of PLSP after laparoscopic sleeve gastrectomy without increasing the associated adverse effects.

Spectrum of Disorders associated with Tetany.

INTRODUCTION: Awareness regarding the etiological spectrum of tetany is poor among physicians. Because of poor awareness, tetany is underdiagnosed and undertreated. MATERIALS AND METHODS: Databases like PubMed, PubMed Central, Scopus, and Google Scholar are searched to identify peer-reviewed articles on tetany. Case reports, case series, and original articles are analyzed to identify different causes of tetany prevalent in the community. Different causes found are analyzed and tabulated, and finally, a flowchart is made on the approach for diagnosing different underlying pathologies of tetany. RESULTS: Both metabolic and respiratory alkalosis are important causes of tetany because of reduced ionized calcium levels. Gitelman syndrome (GS) is associated with metabolic alkalosis, hypokalemia, hypomagnesemia and hypocalciuria, and frequently causes normocalcemic tetany. Recurrent vomiting and primary hyperaldosteronism also cause tetany due to metabolic alkalosis. Hyperventilation syndrome (HVS) leads to respiratory alkalosis and is a frequent cause of tetany. Hyperventilation-induced tetany is also seen after spinal anesthesia and in respiratory disorders like asthma. Vitamin D deficiency (VDD), primary hypoparathyroidism, and pseudohypoparathyroidism (PHP) (1a, 1b, and 2) cause hypocalcemic tetany. Hypomagnesemia causes hypocalcemia and tetany due to peripheral parathyroid hormone resistance and impaired parathyroid hormone secretion. Drugs causing tetany include bisphosphonates, denosumab, cisplatin, antiepileptics, aminoglycosides, diuretics, etc. Tetany is also seen in acute pancreatitis, dengue, falciparum malaria, hyperemesis gravidarum, tumor lysis syndrome (TLS), massive blood transfusion, etc. Conclusion: The spectrum of disorders associated with tetany is diverse. Awareness of different causes will help early and proper diagnosis of tetany.

Transcranial, Non-Invasive Evaluation of Potential Misery Perfusion During Hyperventilation Therapy of Traumatic Brain Injury Patients.

Hyperventilation (HV) therapy uses vasoconstriction to reduce intracranial pressure (ICP) by reducing cerebral blood volume. However, as HV also lowers cerebral blood flow (CBF), it may provoke misery perfusion (MP), in which the decrease in CBF is coupled with increased oxygen extraction fraction (OEF). MP may rapidly lead to the exhaustion of brain energy metabolites, making the brain vulnerable to ischemia. MP is difficult to detect at the bedside, which is where transcranial hybrid, near-infrared spectroscopies are promising because they non-invasively measure OEF and CBF. We have tested this technology during HV (∼30 min) with bilateral, frontal lobe monitoring to assess MP in 27 sessions in 18 patients with traumatic brain injury. In this study, HV did not lead to MP at a group level (p > 0.05). However, a statistical approach yielded 89 events with a high probability of MP in 19 sessions. We have characterized each statistically significant event in detail and its possible relationship to clinical and radiological status (decompressive craniectomy and presence of a cerebral lesion), without detecting any statistically significant difference (p > 0.05). However, MP detection stresses the need for personalized, real-time assessment in future clinical trials with HV, in order to provide an optimal evaluation of the risk-benefit balance of HV. Our study provides pilot data demonstrating that bedside transcranial hybrid near-infrared spectroscopies could be utilized to assess potential MP.

Critical Hypophosphatemia in a Special Operations Combat Dive Candidate: A Case Report.

In contrast to shallow water (hypoxic) blackout and swimming-induced pulmonary edema (SIPE), acute electrolyte disturbance secondary to acute respiratory alkalosis is not considered a common Combat Swimmer injury but has the potential to be life-threatening. We present the case of a 28-year-old Special Operations Dive Candidate who presented to the Emergency Department after a near-drowning incident with altered mental status, generalized weakness, respiratory distress, and tetany. He was found to have severe symptomatic hypophosphatemia (1.00mg/dL) and mild hypocalcemia secondary to intentional hyperventilation between subsurface "cross-overs," causing subsequent acute respiratory alkalosis. This is a unique presentation of a common electrolyte abnormality in a highly specialized population that is self-limiting when caused by acute respiratory alkalosis but poses a significant danger to Combat Swimmers if rescue personnel are not able to respond quickly.

AMPK facilitates the hypoxic ventilatory response through non-adrenergic mechanisms at the brainstem.

We recently demonstrated that the hypoxic ventilatory response (HVR) is facilitated by the AMP-activated protein kinase (AMPK) in catecholaminergic neural networks that likely lie downstream of the carotid bodies within the caudal brainstem. Here, we further subcategorise the neurons involved, by cross-comparison of mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic (TH-Cre) or adrenergic (PNMT-Cre) neurons. As expected, the HVR was markedly attenuated in mice with AMPK-α1/α2 deletion in catecholaminergic neurons, but surprisingly was modestly augmented in mice with AMPK-α1/α2 deletion in adrenergic neurons when compared against a variety of controls (TH-Cre, PNMT-Cre, AMPK-α1/α2 floxed). Moreover, AMPK-α1/α2 deletion in catecholaminergic neurons precipitated marked hypoventilation and apnoea during poikilocapnic hypoxia, relative to controls, while mice with AMPK-α1/α2 deletion in adrenergic neurons entered relative hyperventilation with reduced apnoea frequency and duration. We conclude, therefore, that AMPK-dependent modulation of non-adrenergic networks may facilitate increases in ventilatory drive that shape the classical HVR, whereas AMPK-dependent modulation of adrenergic networks may provide some form of negative feedback or inhibitory input to moderate HVR, which could, for example, protect against hyperventilation-induced hypocapnia and respiratory alkalosis.

Fatal gastrointestinal complications in Pitt-Hopkins syndrome.

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by mutations of the transcription factor 4 (Tcf4) gene. Individuals with PTHS often suffer from severe abdominal bloating and constipation. In this short communication, we discuss two individuals with PTHS who died unexpectedly due to gastrointestinal complications. We aim to increase awareness among healthcare professionals who care for individuals with PTHS, to ensure adequate screening and management of gastrointestinal symptoms in this population. Moreover, we discuss how fatal gastrointestinal complications may be related to PTHS and provide an overview of the literature.

Silent Hypoxemia in COVID-19 Pneumonia.

In patients suffering from Coronavirus Disease 2019 (COVID-19), dyspnoea is less likely to occur despite hypoxemia. Even if the patient develops severe hypoxemia, it cannot be detected from subjective symptoms. In other words, it becomes more serious without the person or the surroundings noticing it. Initially less talked about, hypoxemia without dyspnoea (silent hypoxemia or happy hypoxia: hypoxemia that does not coincide with dyspnoea) is now experienced in many institutions. Dyspnoea is defined as "the unpleasant sensation that accompanies breathing." Dyspnoea occurs when afferent information is transmitted to the sensory area. Receptors involved in the development of dyspnoea include central and peripheral chemoreceptors, chest wall receptors, lung receptors, upper respiratory tract receptors and corollary discharge receptors. In the present study, we considered mechanisms mediating the silent hypoxemia through three cases experienced at our hospital as a dedicated coronavirus treatment hospital. We have treated about 600 people infected with COVID-19, of which about 10% were severe cases. In the present study, the patients' condition was retrospectively extracted and analysed. We investigated three typical cases of COVID-19 pneumonia admitted to our hospital (men and women between the ages of 58 and 86 with hypoxemia and tachypnoea). Silent hypoxemia is not entirely without dyspnoea, but hypoxemia does not cause dyspnoea commensurate with its severity. The virus may have specific effects on the respiratory control system. In our cases, respiratory rate significantly increased with hypoxemia, and hyperventilation occurred. Therefore, information about hypoxemia is transmitted from the carotid body. Since hyperventilation occurs, it is suggested that information is transmitted to effectors such as respiratory muscles. The fact that these patients did not feel the unpleasant sensation indicates that information is not accurately transmitted to the sensory area of the cerebral cortex. These cases suggest that there may be a problem somewhere in the path from the respiratory centre to the sensory area.

Two-handed facemask technique effectively causes hyperventilation in electroconvulsive therapy: an observational study.

BACKGROUND: Electroconvulsive therapy (ECT) remains the mainstay treatment option for patients with psychiatric diseases, such as severe depression. Although various anesthetic techniques provide adequate therapeutic seizures, hyperventilation is a useful adjunct to augment seizure duration and improve seizure quality. We investigated how to efficiently use a facemask to accomplish protocolized hyperventilation and evaluate its effect on ECT seizure. METHODS: We studied 60 patients aged ≥18 years who underwent ECT. The patients were divided into two groups according to the technique of facemask ventilation used: the one-handed (n = 30) and two-handed (n = 30) groups. Following anesthesia induction under preoxygenation conditions, hyperventilation induced hypocapnia in the one-handed facemask group with manual bag ventilation was compared to that in the two-handed facemask group with assisted pressure-controlled ventilation. Ictal and peri-ictal electroencephalogram parameters and cardiovascular responses were monitored and compared between the one-handed and two-handed groups. RESULTS: The two-handed technique demonstrated better electroencephalogram regularity and minimized cardiovascular stress compared to the one-handed technique. These conclusions come from the fact that the one-handed technique induced a substantial volume of leaks around the facemask (201.7 ± 98.6 mL/breath), whereas minimal leaks (25.8 ± 44.6 mL/breath) with stabler and higher ventilation rate led to greater inhaled minute ventilation in the two-handed group (the one-handed group, 9.52 ± 3.94 L/min; the two-handed group, 11.95 ± 2.29 L/min; p <  0.005). At the end of ECT treatment, all parameters of blood pressure and heart rate increased significantly in both groups equally, with lower SpO2 and more ST-segment depression on the electrocardiogram in the one-handed group. Comparing baseline values before anesthesia, ECT treatment significantly depressed ST-segment in both groups, while the degree of depression in ST-segment increased significantly in the one-handed group compared to that in the two-handed group. CONCLUSIONS: End-tidal carbon dioxide monitoring for hyperventilation can reliably ensure hypocapnia only in the two-handed group. In ECT, the two-handed technique assisted by pressure-controlled ventilation is an effective and practical method for hyperventilation to induce adequate therapeutic seizures. While, the two-handed group with sufficient preoxygenation did not cause more cardiovascular stress than the one-handed group. TRIAL REGISTRATION: UMIN Clinical Trials Registry 000046544, Date of registration 05/01/2022.

[Severe respiratory alkalosis due to psychogenic hyperventilation. Report of one case]. / Alcalosis respiratoria grave, la transformación de un cuadro funcional en orgánico. Caso clínico.

Severe respiratory alkalosis is a life-threatening condition, as it induces hypo- calcaemia and extreme adrenergic sensitivity leading to cerebral and myocardial vasoconstriction. We report a 37-year-old woman with previous consultations for a conversion disorder. While she was infected with SARS-CoV-2 (without pulmonary involvement), she consulted in the emergency room due to panic attacks. On admission, she developed a new conversion crisis with progressive clinical deterioration, hyperventilation, and severe respiratory alkalosis (pH 7.68, Bicarbonate 11.8 mEq/L and PaCO2 10 mmHg). Clinically, she was in a coma, with respiratory and heart rates 55 and 180 per min, a blood pressure of 140/90 mmHg, impaired perfusion (generalized lividity, distal coldness, and severe skin mottling) and tetany. She also had electrocardiographic changes and high troponin levels suggestive of ischemia, and hyperlactatemia. She was managed in the hospital with intravenous benzodiazepines. The clinical and laboratory manifestations resolved quickly, without the need for invasive measures and without systemic repercussions.

Diagnostic tests and subtypes of dysfunctional breathing in children with unexplained exertional dyspnea.

BACKGROUND: Inappropriate hyperventilation during exercise may be a specific subtype of dysfunctional breathing (DB). OBJECTIVE: To assess whether Nijmegen questionnaire and hyperventilation provocation test (HVPT) are able to differentiate inappropriate hyperventilation from other DB subtypes in children with unexplained exertional dyspnea, and normal spirometry and echocardiography. METHODS: The results were compared between a subgroup of 25 children with inappropriate hyperventilation (increased V'E/V'CO2 slope during a cardiopulmonary exercise test (CPET)) and an age and sex matched subgroup of 25 children with DB without hyperventilation (median age, 13.5 years; 36 girls). Anxiety was evaluated using State-Trait Anxiety Inventory for Children questionnaire. RESULTS: All children were normocapnic (at rest and peak exercise) and the children with hyperventilation had lower tidal volume/vital capacity on peak exercise (shallow breathing). The Nijmegen score correlated positively with dyspnea during the CPET and the HVPT (p = 0.001 and 0.010, respectively) and with anxiety score (p = 0.022). The proportion of children with a positive Nijmegen score (≥19) did not differ between hyperventilation (13/25) and no hyperventilation (14/25) groups (p = 0.777). Fractional end-tidal CO2 (FETCO2 ) at 5-min recovery of the HVPT was < 90% baseline in all children (25/25) of both subgroups. Likewise, there was no significant difference between the two subgroups for other indices of HVPT (FETCO2 at 3-min recovery and symptoms during the test). CONCLUSION: The validity of the Nijmegen questionnaire and the HVPT to discriminate specific subtypes of dysfunctional breathing, as well as the relevance of the inappropriate hyperventilation subtype itself may both be questioned.

Hyperventilation in functional seizures: Evidence for subtypes.

PURPOSE: Functional seizures (FS) are heterogenous, with no agreed way to subdivide them. One FS subtype frequently observed during EEG is those whose seizures are provoked by hyperventilation. We wished to see whether this subtype might reflect a different seizure mechanism. METHODS: We analysed the video-EEG/ECGs of all patients with FS from two hospitals in Melbourne from 2010-6. RESULTS: We identified 120 patients during the study period, 107 of whom had usable recordings. Examining those 11 (10%) whose seizures had been induced by hyperventilation, we compared the heart rates of those where the seizure occurred during the hyperventilation, and those where they occurred afterwards. The during-hyperventilation group had a higher baseline heart rate which increased prior to their seizure; the after-hyperventilation group had a lower baseline heart rate and no pre-ictal increase. In those patients whose seizures were not hyperventilation-induced, the same two heart rate patterns could be found: those with a higher baseline heart rate showed increasing heart rate prior to seizure onset, while those with a lower baseline heart rate did not. Cluster analysis showed the sample was optimally divided into these two groups based on their pre-onset heart rate alone. CONCLUSION: Patients with FS show two distinct patterns of pre-ictal heart rate, which may reflect two distinct seizure mechanisms.

Hyperventilation-Induced Hypocapnia in an Aviator.

BACKGROUND: Physiological episodes are a top safety concern for aviators across the United States military. While many cases and a variety of causes for physiological episodes have been described, few cases, if any, have been reported of hyperventilation-induced hypocapnia and transient loss of consciousness.CASE REPORT: Here we describe a case of an aviator who experienced tingling extremities, confusion, and loss of consciousness during a flight. The aviator incorrectly believed he was experiencing hypoxia and continued to take multiple steps to troubleshoot the wrong underlying problem for his symptoms. Evaluation after landing suggested this was instead a stress-induced hyperventilation that resulted in symptomatic hypocapnia.DISCUSSION: We report this case to add to the body of literature in understanding this phenomenon as well as to provide aviators, physiologists, and flight surgeons with practical suggestions for recognizing hyperventilation-induced hypocapnia and awareness of how to remedy this situation when they recognize it.Kramer KEP, Anderson EE. Hyperventilation-induced hypocapnia in an aviator. Aerosp Med Hum Perform. 2022; 93(5):470-471.

Excess ventilation and exertional dyspnoea in heart failure and pulmonary hypertension.

Increased ventilation relative to metabolic demands, indicating alveolar hyperventilation and/or increased physiological dead space (excess ventilation), is a key cause of exertional dyspnoea. Excess ventilation has assumed a prominent role in the functional assessment of patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction, pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). We herein provide the key pieces of information to the caring physician to 1) gain unique insights into the seeds of patients' shortness of breath and 2) develop a rationale for therapeutically lessening excess ventilation to mitigate this distressing symptom. Reduced bulk oxygen transfer induced by cardiac output limitation and/or right ventricle-pulmonary arterial uncoupling increase neurochemical afferent stimulation and (largely chemo-) receptor sensitivity, leading to alveolar hyperventilation in HFrEF, PAH and small-vessel, distal CTEPH. As such, interventions geared to improve central haemodynamics and/or reduce chemosensitivity have been particularly effective in lessening their excess ventilation. In contrast, 1) high filling pressures in HFpEF and 2) impaired lung perfusion leading to ventilation/perfusion mismatch in proximal CTEPH conspire to increase physiological dead space. Accordingly, 1) decreasing pulmonary capillary pressures and 2) mechanically unclogging larger pulmonary vessels (pulmonary endarterectomy and balloon pulmonary angioplasty) have been associated with larger decrements in excess ventilation. Exercise training has a strong beneficial effect across diseases. Addressing some major unanswered questions on the link of excess ventilation with exertional dyspnoea under the modulating influence of pharmacological and nonpharmacological interventions might prove instrumental to alleviate the devastating consequences of these prevalent diseases.

C-reactive protein elevation predicts in-hospital deterioration after aneurysmal subarachnoid hemorrhage: a retrospective observational study.

BACKGROUND: There is increasing evidence that inflammation plays a role in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH) and in the development of delayed cerebral ischemia (DCI). However, the assessment and interpretation of classically defined inflammatory parameters is difficult in aSAH patients. The objective of this study was to investigate the relationship between easily assessable findings (hyperventilation, fever, white blood cell count (WBC), and C-reactive protein (CRP)) and the occurrence of DCI and unfavorable neurological outcome at discharge in aSAH patients. METHODS: Retrospective analysis of prospectively collected data from a single center cohort. We evaluated the potential of clinical signs of inflammation (hyperventilation, fever) and simple inflammatory laboratory parameters CRP and WBC to predict unfavorable outcomes at discharge and DCI in a multivariate analysis. A cutoff value for CRP was calculated by Youden's J statistic. Outcome was measured using the modified Rankin score at discharge, with an unfavorable outcome defined as modified Rankin scale (mRS) > 3. RESULTS: We included 97 consecutive aSAH patients (63 females, 34 males, mean age 58 years) in the analysis. Twenty-one (22%) had major disability or died by the time of hospital discharge. Among inflammatory parameters, CRP over 100 mg/dl on day 2 was an independent predictor for worse neurological outcome at discharge. The average C-reactive protein level in the first 14 days was higher in patients with a worse neurological outcome (96.6, SD 48.3 vs 56.3 mg/dl, SD 28.6) in the first 14 days after aSAH. C-reactive protein on day 2 was an indicator of worse neurological outcome. No inflammatory parameter was an independent predictor of DCI. After multivariate adjustment, DCI, increased age, and more than 1 day of mechanical ventilation were significant predictors of worse neurological outcome. CONCLUSIONS: Early elevated CRP levels were a significant predictor of worse neurological outcome at hospital discharge and may be a useful marker of later deterioration in aSAH.

Hyperventilation-induced focal seizures in adults: think autoimmune encephalitis.

Case reports have described rare patients with autoimmune encephalitis in whom focal seizures could be reliably provoked by hyperventilation. With the hypothesis that this phenomenon may have diagnostic significance, all cases of hyperventilation-induced focal seizures identified during ~10,000 consecutive routine electroencephalography (EEG) studies were reviewed, and corresponding diagnoses established. Seven EEG recordings, in six patients, contained focal hyperventilation-induced seizures, each of temporal lobe onset. All patients were diagnosed with autoimmune encephalitis, in two cases after EEG; five had voltage-gated potassium channel complex autoantibodies. Although rare, a hyperventilation-induced focal seizure during EEG in an adult should raise concern for autoimmune encephalitis.

Cheyne-stokes respiration in children with heart failure.

Cheyne-Stokes respiration (CSA-CSR) is a form of central sleep apnea characterized by alternating periods of hyperventilation and central apneas or hypopneas. CSA-CSR develops following a cardiac insult resulting in a compensatory increase in sympathetic activity, which in susceptible patients causes hyperventilation and destabilizes respiratory control. The physiological changes that occur in CSA-CSR include hyperventilation, a reduced blood gas buffering capacity, and circulatory delay. In adults, 25% to 50% of patients with heart failure are reported to have CSA-CSR. The development of CSA-CSR in this group of patients is considered a poor prognostic sign. The prevalence, progression, and treatment outcomes of CSA-CSR in children remain unclear with only 11 children being described in the literature. The lack of data is possibly not due to the paucity of children with severe heart failure and CSA-CSR but because they may be under-recognized, compounded by the absence of routine polysomnographic assessment of children with moderate to severe heart failure. Building on much broader experience in the diagnosis and management of CSA-CSR in adult sleep medicine and our limited experience in a pediatric quaternary center, this paper will discuss the prevalence of CSA-CSR, its' treatment options, outcomes in children, and the potential future direction for research in this understudied area of pediatric sleep medicine.

[Viral meningitis: a rare cause of hyperventilation]. / Virale Meningoenzephalitis: eine seltene Ursache der Hyperventilation.

The etiology of hyperventilation is multifactorial. When excluding somatic causes, neurogenic hyperventilation must always be considered. Since hyperventilation itself causes neuromuscular symptoms such as paresthesia, vertigo, cephalgia, and nausea, the differential diagnosis of viral meningitis in the presence of hyperventilation is not always obvious and can easily be overlooked. Our case report shows that somatogenic causes of hyperventilation should be carefully excluded.