Reduced Stroke Volume and Brain Perfusion Drive Postural Hyperventilation in Postural Orthostatic Tachycardia Syndrome.

Postural hyperventilation has been implicated as a cause of postural orthostatic tachycardia syndrome (POTS), yet the precise mechanisms underlying the heightened breathing response remain unclear. This study challenges current hypotheses by revealing that exaggerated peripheral chemoreceptor activity is not the primary driver of postural hyperventilation. Instead, significant contributions from reduced stroke volume and compromised brain perfusion during orthostatic stress were identified. These findings shed light on our understanding of POTS pathophysiology, emphasizing the critical roles of systemic hemodynamic status. Further research should explore interventions targeting stroke volume and brain perfusion for more effective clinical management of POTS.

The complexity of cerebral blood flow regulation: the interaction of posture and vasomotor reactivity.

Arterial carbon dioxide ([Formula: see text]) and posture influence the middle (MCAv) and posterior (PCAv) cerebral artery blood velocities, but there is paucity of data about their interaction and need for an integrated model of their effects, including dynamic cerebral autoregulation (dCA). In 22 participants (11 males, age 30.2 ± 14.3 yr), blood pressure (BP, Finometer), dominant MCAv and nondominant PCAv (transcranial Doppler ultrasound), end-tidal CO2 (EtCO2, capnography), and heart rate (HR, ECG) were recorded continuously. Two recordings (R) were taken when the participant was supine (R1, R2), two taken when the participant was sitting (R3, R4), and two taken when the participant was standing (R5, R6). R1, R3, and R5 consisted of 3 min of 5% CO2 through a mask and R2, R4, and R6 consisted of 3 min of paced hyperventilation. The effects of [Formula: see text] were expressed with a logistic curve model (LCM) for each parameter. dCA was expressed by the autoregulation index (ARI), derived by transfer function analysis. Standing shifted LCM to the left for MCAv (P < 0.001), PCAv (P < 0.001), BP (P = 0.03), and ARI (P = 0.001); downward for MCAv and PCAv (both P < 0.001), and upward for HR (P < 0.001). For BP, LCM was shifted downward by sitting and standing (P = 0.024). For ARI, the hypercapnic range of LCM was shifted upward during standing (P < 0.001). A more complete mapping of the combined effects of posture and arterial CO2 on the cerebral circulation and peripheral variables can be obtained with the LCM over a broad physiological range of EtCO2 values.NEW & NOTEWORTHY Data from supine, sitting, and standing postures were measured. Modeling the data with logistic curves to express the effects of CO2 reactivity on middle cerebral artery blood velocity (MCAv), posterior cerebral artery blood velocity (PCAv), heart rate, blood pressure (BP), and the autoregulation index (ARI), provided a more comprehensive approach to study the interaction of arterial CO2 with posture than in previous studies. Above all, shifts of the logistic curve model with changes in posture have shown interactions with [Formula: see text] that have not been previously demonstrated.

Unraveling persistent dyspnea after mild COVID: insights from a case series on hyperventilation provocation tests.

Dyspnea is a common yet poorly understood symptom of long COVID, affecting many patients. This brief report examines the role of dysfunctional breathing in persistent dyspnea among patients with mild post-COVID-19 using hyperventilation provocation tests (HVPT). In this case series, six patients with unexplained dyspnea and normal cardiopulmonary function underwent HVPT. Despite normal exercise testing results, all patients exhibited delayed PETCO2 recovery, indicative of a hyperventilation pattern consistent with chronic hyperventilation syndrome, without typical symptomatic manifestations. These findings suggest underlying post-COVID respiratory dysregulation, emphasizing the importance of targeted diagnostic and therapeutic approaches for persistent respiratory symptoms in long COVID patients.

A Review of Hyperventilation Activation in Diagnosis and Management of Childhood Absence Epilepsy.

Childhood absence epilepsy is one of the most prevalent pediatric epilepsy syndromes, but diagnostic delay is common and consequential. Childhood absence epilepsy is diagnosed by history and physical examination including hyperventilation with electroencephalography (EEG) used to confirm the diagnosis. Hyperventilation produces generalized spike-wave discharges on EEG in >90% of patients with childhood absence epilepsy and provokes clinical absence seizures consisting of brief loss of consciousness typically within 90 seconds. Child neurologists report a high volume of referrals for children with "staring spells" that strain already limited health care resources. Resources are further strained by the use of EEG for monitoring antiseizure medication effectiveness with unclear benefit. In this review, we examine the safety and efficacy of hyperventilation activation as a tool for the diagnosis and management of childhood absence seizures.

[Dyspnea in post-COVID-19 patients: A review].

New coronavirus infection may lead to long-term consequences, particularly to post-COVID syndrome, one of the most common manifestations of which is dyspnea. Post-COVID-19 shortness of breath may persist from one to several months and even years that results in low quality of life of patients. The review highlights possible risk factors and causes of dyspnea in post-COVID period such as lung damage, cardiovascular pathology, hyperventilation syndrome, dysfunction of the autonomic nervous system, detraining, anemia, etc. The authors present data about COVID-19-associated causes of dyspnea and severity of acute COVID-19. The review emphasizes the importance of a multidisciplinary approach to the diagnosis and treatment of patients with shortness of breath in post-COVID-19 period.

[Artificial ventilation in patients with stroke: main results of the Russian multicenter observational clinical trial RETAS]. / Iskusstvennaya ventilyatsiya legkikh u patsientov s ostrym narusheniem mozgovogo krovoobrashcheniya: osnovnye rezul'taty Rossiiskogo mnogotsentrovogo observatsionnogo klinicheskogo issledovaniya RETAS.

OBJECTIVE: To analyze the relationship between the characteristics of respiratory support (RS) for patients with stroke and clinical factors with the number and structure of complications, deaths, and length of stay in the intensive care unit (ICU) and duration of artificial pulmonary ventilation (ALV). MATERIAL AND METHODS: The Russian multicenter observational clinical study «Respiratory Therapy for Acute Stroke¼ (RETAS) that enrolled 1289 patients with stroke requiring RS was conducted under the auspices of the All-Russian public organization «Federation of Anesthesiologists and Resuscitators¼. Indications for ALV, the use of hyperventilation, the maximum level of positive end-expiratory pressure, starting modes of mechanical ventilation, timing of tracheostomy, the incidence of protein-energy malnutrition (PEM) and infectious complications were analyzed. The following scales were used to assess the severity of the condition: the National Institutes of Health Stroke Severity Scale (NIHSS), the Glasgow Coma Scale, the Glasgow Outcome Scale (GOS). RESULTS: For the group of patients with a stroke severity of more than 20 NIHSS points, the mortality increase was associated with initial hypoxia (p=0.004), hyperventilation used to relieve intracranial hypertension (p=0.034), and starting ventilation with volume control (VC) compared with starting pressure-controlled ventilation (PC) (p<0.001). We found that the use of the instrumental monitoring of intracranial pressure was associated with a decrease in mortality (p<0.001). The absence of PEM in patients with stroke is associated with a higher probability of a positive outcome (GOS 4 and 5) for the group with NIHSS less than 14 points (p<0.001). Ventilator-associated tracheobronchitis and ventilator-associated pneumonia were associated with an increase in the duration of ALV, the duration of weaning from the ventilator (for ventilator-associated tracheobronchitis) and the duration of stay in the ICU, and also reduced the chances of favorable outcomes (p<0.05). CONCLUSION: The factors associated with increased mortality in acute stroke are: hypoxemia at the start of ALV, hyperventilation, starting ventilation with VC in comparison with starting ventilation with PC, the use of only clinical methods of monitoring intracranial pressure in comparison with instrumental monitoring. The adverse effect of PEM and infectious complications on the outcome in patients with acute stroke has been proven.

[Lung function during normal pregnancy]. / Particularités de la physiologie respiratoire au cours de la grossesse normale.

Pregnancy is associated with major changes in hormonal status, anatomy and physiology involving all systems of a human organism. This narrative review focuses on the most recent data concerning lung function changes during healthy pregnancy. The major findings are as follows: pregnancy is associated with a reduction in static lung volumes reaching 20% of residual functional capacity; it is also associated with chronic alveolar hyperventilation; lastly, it is not associated with significant changes in variables measured by spirometry such as vital capacity, forced expiratory volume in one second and peak expiratory flow, or airway resistance.

Postoperative Symptomatic Cerebral Vasospasm: Requiring Attention Following an Uneventful Resection of an Epidermoid Cyst - A Case Report and Literature Review.

Cerebral vasospasm associated with epidermoid cyst can be caused by tumor content spillage, such as spontaneous rupture and postsurgical resection. Symptomatic cerebral vasospasm following the resection of an intracranial epidermoid cyst is a rare but serious complication that lacks a consensus on treatment. Case presentation: A 10-year-old girl underwent an uneventful complete resection of a left cerebellopontine angle epidermoid cyst. On the second postoperative day (POD 2), she exhibited reduced speech, confusion, and hyperventilation followed by hypocapnia. On POD 4, she developed right hemiparesis and dysphasia. Cerebral magnetic resonance imaging showed restricted diffusion areas in her left temporal and parietal lobes and the dorsal thalamus. Magnetic resonance angiograms confirmed narrowing of the proximal middle cerebral arteries, consistent with vasospasm. Conservative management, consisting of intravenous hydration and corticosteroid administration, proved effective in resolving her symptoms and radiologic vasospasm. On POD 8, the extensive restricted diffusion areas notably decreased in size. Her right hemiparesis was completely resolved, and her dysphasia gradually improved over time. At the 1-year follow-up, she exhibited moderate transcortical sensory dysphasia. To our knowledge, this study is the first to report on a pediatric case of symptomatic cerebral vasospasm following an epidermoid cyst resection. The combination of tumor content spillage and hyperventilation may contribute to the occurrence of cerebral vasospasm and subsequent ischemia. This complication should be acknowledged after a complete and uneventful resection.

The effect of acute respiratory demand on postural control: A systematic review.

BACKGROUND: Postural control can be challenged by breathing. RESEARCH QUESTION: What is the effect of an acute increase in respiratory demand on postural control compared to quiet breathing? METHODS: A systematic review was conducted. Electronic databases were systematically searched until October 18, 2022 on studies reporting changes in center of pressure (CoP) motion related to an acute manipulation of respiratory demand compared to quiet breathing during upright standing in healthy participants and/or participants with a clinical condition. RESULTS: Twenty-one studies in healthy participants showed that voluntary (not metabolic-induced) hyperventilation or inspiratory resistive loading significantly increased CoP motion, while breath-holding decreased CoP motion, compared to quiet breathing (p< 0.05). Manipulating respiratory rate or breathing patterns did not reveal consistent results. Four studies showed that people with low back pain showed similar CoP responses to increasing respiratory demand (p> 0.05), except for breathing at different rates, whereas they showed greater CoP motion during quiet breathing. SIGNIFICANCE: The extent of postural disturbance depended on the breathing mode and how it was quantified (i.e., CoP coupled with breathing movement or overall CoP measures). Voluntary hyperventilation and inspiratory resistive loading increased postural sway. For voluntary hyperventilation, this could be explained by CoP motion being directly coupled to chest wall movements whereas metabolic-induced hyperventilation did not increase CoP motion or CoP coupling with breathing. Breath-holding decreased postural sway. Patients with low back pain show greater postural sways than pain-free individuals during quiet breathing, although they exhibit similar postural adaptations to respiratory-related challenges as controls.

The effect of probiotics and casein supplementation on aerobic capacity parameters of male soccer players.

BACKGROUND: In the realm of sports science, nutrition is a well-established pillar for athletes' training, performance, and post-workout recovery. However, the role of gut microbiota, often overlooked, is a novel and intriguing aspect that can significantly impact athletic performance. With this in mind, our study ventures into uncharted territory, investigating the effect of probiotic and casein supplementation on the aerobic capacity of male soccer players. METHOD: A double-blinded and placebo-controlled study was conducted with 44 male soccer players (Age: 22.81 ± 2.76 yr, Height: 177.90 ± 6.75 cm, Weight: 67.42 ± 8.44 kg). The participants were subjected to the Bruce test in the beginning; then, they were randomly divided into four groups, each consisting of 11 people: probiotics (PRO), casein (CAS), probiotics with casein (PRO+CAS), and placebo (PLA). PRO group was given one probiotic capsule (containing strains of Lactiplantibacillus plantarum BP06, Lacticaseibacillus casei BP07, Lactobacillus acidophilus BA05, Lactobacillus delbrueckii BD08 bulgaricus, Bifidobacterium infantis BI04, Bifidobacterium longum BL03, Bifidobacterium breve BB02 and Streptococcus salivarius thermophilus BT01, with a total dose of 4.5 × 1011 CFU) during dinner, while the CAS group consumed 20 grams of casein powder 45 minutes before bed. The PRO+CAS group was given one probiotic capsule during dinner and 20 grams of casein powder 45 minutes before bed. The participants in the PLA group were given one red capsule (containing 5 grams of starch) during dinner. All participants were instructed to take the supplements only on training days, three times a week for four weeks. The maximal oxygen consumption (VO2max), Ventilatory Threshold (VT), Time-to-exhaustion (TTE), Respiratory Compensation Point (RCP), Isocapnic area Time (Time-IC), Isocapnic area oxygen consumption (VO2-IC), and Hypocapnic Hyperventilation area Time (Time-HHV), after the Bruce test were Measured. All data were analyzed using SPSS Windows software, mixed repeated measure ANOVA, and Bonferroni post hoc test at p < 0.05 level. RESULTS: The current study's findings illustrated that, after the intervention, TTE (p = 0.01) and RCP (p = 0.01) were significantly improved in PRO+CAS compared to the PLA group. No significant difference was observed between PRO and PLA (p = 0.52), PRO and CAS (p = 0.999), PRO and PRO+CAS (p = 0.9), CAS and PLA (p = 0.65), CAS and PRO+CAS (p = 0.73) in TTE. In addition, no significant difference was observed between PRO and CAS (p = 0.999), PRO and PLA (p = 0.40), PRO and PRO+CAS (p = 0.999), CAS and PLA (p = 0.263), CAS and PRO+CAS (p = 0.999) in RCP. Time-HHV was significantly higher in PRO+CAS (p = 0.000) and CAS (p = 0.047) compared to the PLA group. However, no significant difference was observed in the Time-HHV between PRO and CAS (p = 0.999), PRO and PRO+CAS (p = 0.25), PRO and PLA (p = 0.12), and CAS and PRO+CAS (p = 0.57). Additionally, all the groups had no significant differences in VO2max, VT1, VO2-IC and Time-IC. CONCLUSION: The findings showed that consuming probiotics and casein could relatively improve the aerobic capacity of male soccer players. Nevertheless, simultaneous consumption of probiotics and casein had a more pronounced effect on aerobic capacity indicators, especially TTE and Time-HHV.

The effect of CO2 on the age dependence of neurovascular coupling.

Prior studies have identified variable effects of aging on neurovascular coupling (NVC). Carbon dioxide (CO2) affects both cerebral blood velocity (CBv) and NVC, but the effects of age on NVC under different CO2 conditions are unknown. Therefore, we investigated the effects of aging on NVC in different CO2 states during cognitive paradigms. Seventy-eight participants (18-78 yr), with well-controlled comorbidities, underwent continuous recordings of CBv by bilateral insonation of middle (MCA) and posterior (PCA) cerebral arteries (transcranial Doppler), blood pressure, end-tidal CO2, and heart rate during poikilocapnia, hypercapnia (5% CO2 inhalation), and hypocapnia (paced hyperventilation). Neuroactivation via visuospatial (VS) and attention tasks (AT) was used to stimulate NVC. Peak percentage and absolute change in MCAv/PCAv, were compared between CO2 conditions and age groups (≤30, 31-60, and >60 yr). For the VS task, in poikilocapnia, younger adults had a lower NVC response compared with older adults [mean difference (MD): -7.92% (standard deviation (SD): 2.37), P = 0.004], but comparable between younger and middle-aged groups. In hypercapnia, both younger [MD: -4.75% (SD: 1.56), P = 0.009] and middle [MD: -4.58% (SD: 1.69), P = 0.023] age groups had lower NVC responses compared with older adults. Finally, in hypocapnia, both older [MD: 5.92% (SD: 2.21), P = 0.025] and middle [MD: 5.44% (SD: 2.27), P = 0.049] age groups had greater NVC responses, compared with younger adults. In conclusion, the magnitude of NVC response suppression from baseline during hyper- and hypocapnia, did not differ significantly between age groups. However, the middle age group demonstrated a different NVC response while under hypercapnic conditions, compared with hypocapnia.NEW & NOTEWORTHY This study describes the effects of age on neurovascular coupling under altered CO2 conditions. We demonstrated that both hypercapnia and hypocapnia suppress neurovascular coupling (NVC) responses. Furthermore, that middle age exhibits an NVC response comparable with younger adults under hypercapnia, and older adults under hypocapnia.

Heartbeat-evoked potentials following voluntary hyperventilation in epilepsy patients: respiratory influences on cardiac interoception.

Introduction: Current evidence indicates a modulating role of respiratory processes in cardiac interoception, yet whether altered breathing patterns influence heartbeat-evoked potentials (HEP) remains inconclusive. Methods: Here, we examined the effects of voluntary hyperventilation (VH) as part of a clinical routine examination on scalp-recorded HEPs in epilepsy patients (N = 80). Results: Using cluster-based permutation analyses, HEP amplitudes were compared across pre-VH and post-VH conditions within young and elderly subgroups, as well as for the total sample. No differences in the HEP were detected for younger participants or across the full sample, while an increased late HEP during pre-VH compared to post-VH was fond in the senior group, denoting decreased cardiac interoceptive processing after hyperventilation. Discussion: The present study, thus, provides initial evidence of breathing-related HEP modulations in elderly epilepsy patients, emphasizing the potential of HEP as an interoceptive neural marker that could partially extend to the representation of pulmonary signaling. We speculate that aberrant CO2-chemosensing, coupled with disturbances in autonomic regulation, might constitute the underlying pathophysiological mechanism behind the obtained effect. Available databases involving patient records of routine VH assessment may constitute a valuable asset in disentangling the interplay of cardiac and ventilatory interoceptive information in various patient groups, providing thorough clinical data to parse, as well as increased statistical power and estimates of effects with higher precision through large-scale studies.

Hypocapnia in women with fibromyalgia.

OBJECTIVES: The purpose of this study was to investigate whether people with fibromyalgia (FM) have dysfunctional breathing by examining acid-base balance and comparing it with healthy controls. METHODS: Thirty-six women diagnosed with FM and 36 healthy controls matched for age and gender participated in this cross-sectional study. To evaluate acid-base balance, arterial blood was sampled from the radial artery. Carbon dioxide, oxygen, bicarbonate, base excess, pH and lactate were analysed for between-group differences. Blood gas analyses were performed stepwise on each individual to detect acid-base disturbance, which was categorized as primary respiratory and possible compensation indicating chronicity. A three-step approach was employed to evaluate pH, carbon dioxide and bicarbonate in this order. RESULTS: Women with FM had significantly lower carbon dioxide pressure (p = 0.013) and higher lactate (p = 0.038) compared to healthy controls at the group level. There were no significant differences in oxygen pressure, bicarbonate, pH and base excess. Employing a three-step acid-base analysis, 11 individuals in the FM group had a possible renally compensated mild chronic hyperventilation, compared to only 4 among the healthy controls (p = 0.042). CONCLUSIONS: In this study, we could identify a subgroup of individuals with FM who may be characterized as mild chronic hyperventilators. The results might point to a plausible dysfunctional breathing in some women with FM.

Hyperventilation Syndrome and Hypocalcemia: A Unique Case in Autism Spectrum Disorder.

This case report delves into the rare occurrence of hyperventilation syndrome (HVS) with hypocalcemia in an 18-year-old female diagnosed with autism spectrum disorder (ASD). The rare occurrence highlights the importance of recognizing the potential association between HVS, hypocalcemia, and ASD, emphasizing the need for comprehensive evaluation and management strategies in individuals with ASD presenting with unusual symptoms. Despite ongoing psychotherapeutic treatment, the patient's clinical examination revealed ASD-related communication anomalies. Treatment with Escitalopram resolved panic attacks but left residual anxiety. During an emergency room visit for menstrual-related abdominal pain, a hyperventilation crisis ensued, leading to respiratory alkalosis and hypocalcemia. Swift intervention, including closed mask ventilation and electrolyte infusion, successfully alleviated symptoms. Follow-up assessments indicated normal thyroid function and vitamin D levels. The case highlights the necessity for clinicians to consider electrolyte imbalances in anxiety attacks among ASD patients, emphasizing the importance of timely management for patient safety. The intricate interplay between hyperventilation syndrome, anxiety, and hypocalcemia in ASD patients is explored, offering valuable insights for the nuanced understanding and comprehensive assessment of such cases.

Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge.

BACKGROUND: SARS-CoV-2 infection has raised concerns about long-term health repercussions. Exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequela, potentially impacting respiratory and cardiovascular health. This study aims to assess the long-term presence of EVin after 34 months and its association with cardiorespiratory health in post-COVID patients. METHODS: In a longitudinal study on 32 selected post-COVID subjects, we performed two cardiopulmonary exercise tests (CPETs) at 6 months (T0) and 34 months (T1) after hospital discharge. The study sought to explore the long-term persistence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Measurements included also V̇O2peak, end-tidal pressure of CO2 (PETCO2) levels, oxygen uptake efficiency slope (OUES) and other cardiorespiratory parameters, with statistical significance set at p < 0.05. The presence of EVin at both T0 and T1 defines a persisting EVin (pEVin). RESULTS: Out of the cohort, five subjects (16%) have pEVin at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO and oxygen pulse, suggesting a recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES and Evin in post-COVID follow-ups. CONCLUSIONS: The study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

Evolution of Hyperventilation-Induced Nystagmus in Acute Unilateral Vestibulopathy-Interpretative Model and Etiopathogenetic Hypotheses.

Hyperventilation induces metabolic changes that can elicit nystagmus (hyperventilation-induced nystagmus, HVIN) in various vestibular disorders, revealing vestibular imbalance and bringing out central or peripheral asymmetries. In acute unilateral vestibulopathy (AUVP, namely vestibular neuritis), hyperventilation can induce different patterns of nystagmus (excitatory, inhibitory, or negative), disclosing or modifying existing static vestibular asymmetries through its ability to invalidate compensation or increase peripheral excitability. In this context, we followed the evolutionary stages of HVIN in AUVP across 35 consecutive patients, with the goal of assessing alterations in the oculomotor pattern caused by hyperventilation over time. In the acute phase, the incidence of the excitatory pattern (and the strongly excitatory one, consisting of a reversal nystagmus evoked by hyperventilation) was significantly higher compared to the inhibitory pattern; then, a progressive reduction in the incidence of the excitatory pattern and a concomitant gradual increase in the incidence of the inhibitory one were observed in the follow-up period. Assuming the role of the ephaptic effect and the transient loss of vestibular compensation as opposing mechanisms, i.e., excitatory and inhibitory, respectively, the oculomotor pattern evoked by hyperventilation is the result of the interaction of these two factors. The data obtained allowed us to hypothesize an interpretative model regarding the pathogenetic aspects of responses evoked by hyperventilation and the etiologies of the disease: according to our hypotheses, the excitatory pattern implies a neuritic (viral) form of AUVP; instead, the inhibitory (and negative) one can be an expression of both the neuritic (viral) and vascular forms of the disease.

Common pitfalls in the use of hypertonic sodium bicarbonate for cardiac toxic drug poisonings.

BACKGROUND: Hypertonic sodium bicarbonate is advocated for the treatment of sodium channel blocker poisoning, but its efficacy varies amongst different sodium channel blockers. This Commentary addresses common pitfalls and appropriate usage of hypertonic sodium bicarbonate therapy in cardiotoxic drug poisonings. SODIUM BICARBONATE WORKS SYNERGISTICALLY WITH HYPERVENTILATION: Serum alkalinization is best achieved by the synergistic effect of hypertonic sodium bicarbonate and hyperventilation (PCO2 ∼ 30-35 mmHg [0.47-0.6 kPa]). This reduces the dose of sodium bicarbonate required to achieve serum alkalinization (pH ∼ 7.45-7.55) and avoids adverse effects from excessive doses of hypertonic sodium bicarbonate. VARIABILITY IN RESPONSE TO SODIUM BICARBONATE TREATMENT: Tricyclic antidepressant poisoning responds well to sodium bicarbonate therapy, but many other sodium channel blockers may not. For instance, drugs that block the intercellular gap junctions, such as bupropion, do not respond well to alkalinization. For sodium channel blocker poisonings in which the expected response is unknown, a bolus of 1-2 mmol/kg sodium bicarbonate can be used to assess the response to alkalinization. SODIUM BICARBONATE CAN EXACERBATE TOXICITY FROM DRUGS ACTING ON MULTIPLE CARDIAC CHANNELS: Hypertonic sodium bicarbonate can cause electrolyte abnormalities such as hypokalaemia and hypocalcaemia, leading to QT interval prolongation and torsade de pointes in poisonings with drugs that have mixed sodium and potassium cardiac channel properties, such as hydroxychloroquine and flecainide. THE GOAL FOR HYPERTONIC SODIUM BICARBONATE IS TO ACHIEVE THE ALKALINIZATION TARGET (∼PH 7.5), NOT COMPLETE CORRECTION OF QRS COMPLEX PROLONGATION: Excessive doses of hypertonic sodium bicarbonate commonly occur if it is administered until the QRS complex duration is < 100 ms. A prolonged QRS complex duration is not specific for sodium channel blocker toxicity. Some sodium channel blockers do not respond, and even when there is a response, it takes a few hours for the QRS complex duration to return completely to normal. In addition, QRS complex prolongation can be due to a rate-dependent bundle branch block. So, no further doses should be given after achieving serum alkalinization (pH ∼ 7.45-7.55). MAXIMAL DOSING FOR HYPERTONIC SODIUM BICARBONATE: A further strategy to avoid overdosing patients with hypertonic sodium bicarbonate is to set maximum doses. Exceeding 6 mmol/kg is likely to cause hypernatremia, fluid overload, metabolic alkalosis, and cerebral oedema in many patients and potentially be lethal. RECOMMENDATION FOR THE USE OF HYPERTONIC SODIUM BICARBONATE IN SODIUM CHANNEL BLOCKER POISONING: We propose that hypertonic sodium bicarbonate therapy be used in patients with sodium channel blocker poisoning who have clinically significant toxicities such as seizures, shock (systolic blood pressure < 90 mmHg, mean arterial pressure <65 mmHg) or ventricular dysrhythmia. We recommend initial bolus dosing of hypertonic sodium bicarbonate of 1-2 mmol/kg, which can be repeated if the patient remains unstable, up to a maximum dose of 6 mmol/kg. This is recommended to be administered in conjunction with mechanical ventilation and hyperventilation to achieve serum alkalinization (PCO2∼30-35 mmHg [4-4.7 kPa]) and a pH of ∼7.45-7.55. With repeated bolus doses of hypertonic sodium bicarbonate, it is imperative to monitor and correct potassium and sodium abnormalities and observe changes in serum pH and on the electrocardiogram. CONCLUSIONS: Hypertonic sodium bicarbonate is an effective antidote for certain sodium channel blocker poisonings, such as tricyclic antidepressants, and when used in appropriate dosing, it works synergistically with hyperventilation to achieve serum alkalinization and to reduce sodium channel blockade. However, there are many pitfalls that can lead to excessive sodium bicarbonate therapy and severe adverse effects.