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.

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.

Bidirectional ventricular tachycardia induced by respiratory alkalosis mediated hypokalemia in a patient with acute ischemic heart failure.

Bidirectional ventricular tachycardia (BVT) is a rare arrhythmia that is generally observed in patients with catecholaminergic ventricular tachycardia or digoxin overdose. Herein, we present a case of BVT and electrical storm (ES) in an acute ischemic heart failure patient that is typically induced by hypokalemia. The patient was in invasive mechanical ventilator (MV) support and hypokalemia was related to acute respiratory alkalosis and that caused refractory hypokalemia despite intravenous (IV) potassium replacement. We also discuss our approach to solve refractory hypokalemia caused by respiratory alkalosis.

Comparative analysis between available challenge tests in the hyperventilation syndrome.

BACKGROUND: The hyperventilation syndrome (HVS) is characterized by somatic/ psychological symptoms due to sustained hypocapnia and respiratory alkalosis without any organic disease. OBJECTIVE: The purpose of this study was to compare ventilatory parameters and symptoms reproducibility during the hyperventilation provocation test (HVPT) and cardiopulmonary exercise test (CPET) as diagnostic tools in patients with HVS, and to identify the most frequent etiologies of the HVS by a systematic assessment. METHODS: After exclusion of organic causes, 59 patients with HVS according to Nijmegen's questionnaire (NQ) score ≥23 with associated hypocapnia (PaCO2/PETCO2<35 mm Hg) were studied. RESULTS: The most frequent comorbidities of HVS were anxiety and asthma (respectively 95% and 73% of patients). All patients described ≥3 symptoms of NQ during the HVPT vs 14% of patients during the CPET (p<0.01). For similar maximal ventilation (61 L/min during HVPT vs 60 L/min during CPET), the median level of PETCO2 decreased from 30 mmHg at baseline to 15 mmHg during hyperventilation and increased from 31 mmHg at baseline to 34 mmHg at peak exercise (all p<0.01). No significant difference for the ventilatory parameters was found between patients with HVS (n = 16) and patients with HVS + asthma (n = 43). CONCLUSIONS: In term of symptoms reproducibility, HVPT is a better diagnostic tool than CPET for HVS. An important proportion of patients with HVS has an atypical asthma previously misdiagnosed. The exercise-induced hyperventilation did not induce abnormal reduction in PETCO2, suggesting that the exercise could be a therapeutic tool in HVS.

Study of Acid-Base Disorders and Biochemical Findings of Patients in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Acid base disorder is a condition characterized by alteration in blood pH by the imbalance between the components of blood leading to a life threatening situation. The main aim of this study was to find the prevalence of acid-base disorders and biochemical findings of such disorders in patients in a tertairy care hospital. METHODS: This descriptive cross-sectional study was conducted in Nobel Medical College Teaching Hospital from 1st September, 2018 to 31st August, 2019. Ethical apporoval was taken from Institutional Review Committee. All the patients presented to emergency department, intensive care units and wards were included during the study period. Data were entered and calculations were done in Microsoft Excel, point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Out of arterial blood gas analysis of 1144 patients, the prevalence of acid base disorders was 718 (62.76%) at 95% Confidence Interval (59.96-65.56%). Simple and mixed acid base disorders were observed in 332 (46.24%) and 386 (53.76%) patients respectively. Respiratory alkalosis was most common among 134 (40.36%) cases in simple acid base disorder whereas metabolic acidosis and respiratory alkalosis was most common among 204 (52.85%) in mixed acid base disorder. All types of disorders were observed more in elderly people (41-60 and >60 age group) than other age groups. CONCLUSIONS: Acid base disorder was found to be more common in very ill patients in emergency and intensive care units. Mixed acid base disorder was the most common with male and elderly patients in predominance.

Respiratory alkalosis may impair the production of vitamin D and lead to significant morbidity, including the fibromyalgia syndrome.

Hyperventilation caused by physical and/or psychological stress may lead to significant respiratory alkalosis and an elevated systemic pH. The alkalotic pH may in turn suppress the normal renal release of phosphate into the urine, thereby interrupting the endogenous production of 1,25-dihydroxyvitamin D (calcitriol). This could cause a shortfall in its normal production, leading to a variety of adverse consequences. It might partially explain the pathogenesis of acute mountain sickness, a treatable disease characterized by severe hyperventilation secondary to the hypoxia of high altitude exposure. Milder degrees of hyperventilation due to different forms of stress may produce other conditions which share characteristics with acute mountain sickness. One of these may be the fibromyalgia syndrome, a chronic painful disorder for which no satisfactory treatment exists. Should fibromyalgia and acute mountain sickness have a common etiology, may they also share a common form of treatment? Evidence is presented to support this hypothesis.

Microangiopatía trombótica en el anciano. A propósito de un caso / Thrombotic microangiophaty in elderly. Case report

No disponible

Hyperventilation of pregnancy presenting with flaccid quadriparesis due to hypokalaemia secondary to respiratory alkalosis.

Hyperventilation in pregnancy is a cause of chronic respiratory alkalosis. Alkalosis either metabolic or respiratory may cause intracellular shift of potassium ions that may lead to hypokalaemia. However, the resultant hypokalaemia in respiratory alkalosis is usually mild and does not cause much clinical features. A five-months-pregnant female of the age 25 years presented with sudden onset flaccid weakness of both lower limbs associated with thigh muscle pain followed by weakness of both upper limbs within three days. Subsequent investigation revealed severe hypokalaemia due to acute exacerbation of chronic respiratory alkalosis secondary to hyperventilation of pregnancy, other causes of hypokalaemia being ruled out. Respiratory alkalosis causes tetany and other clinical manifestations. But hypokalaemia and such weakness is rarely found. Thisis probably the first report of this type from India.

Hyperventilation provokes symptoms of carpal tunnel syndrome.

Hyperventilation causes respiratory alkalosis. The nervous system is more excitable in alkalosis. This phenomenon can be observed as paraesthesia in fingers and toes as well as around the lips in anxious patients breathing rapidly. We wanted to test this phenomenon on already irritable nerves like the median nerve in carpal tunnel syndrome (CTS). We deployed 50 patients who came in to the day case unit for carpal tunnel decompression with electro-physiologically proven diagnosis. We devised a test whereby patients were made to hyperventilate under prescribed conditions and repeated Phalen's test and Tinel's sign for comparison. These were compared with a control group chosen randomly among hospital staff. 86% patients had a positive result which was just behind Phalen's test in sensitivity. It was also 100% specific as there were no false positives. Hyperventilation is a phenomenon which provokes carpal tunnel syndrome. Its clinical value remains to be seen due to cumbersome method and probable patient non-compliance but it is a new discovery. It may be useful in other irritable-nerve-syndromes as a test to add to our available armament. It may be an additional factor or a primary reason for nocturnal paraesthesias in CTS patients.

Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation.

BACKGROUND: Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. METHODS: Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO(2) and PaCO(2) and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. RESULTS: Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis-metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1 ± 9.8, 36.2 ± 8.9 and 53.3 ± 4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis-metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. CONCLUSIONS: Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.

Respiratory alkalosis in children with febrile seizures.

PURPOSE: Febrile seizures (FS) are the most common type of convulsive events in children. FS are suggested to result from a combination of genetic and environmental factors. However, the pathophysiologic mechanisms underlying FS remain unclear. Using an animal model of experimental FS, it was demonstrated that hyperthermia causes respiratory alkalosis with consequent brain alkalosis and seizures. Here we examine the acid-base status of children who were admitted to the hospital for FS. Children who were admitted because of gastroenteritis (GE), a condition known to promote acidosis, were examined to investigate a possible protective effect of acidosis against FS. METHODS: We enrolled 433 age-matched children with similar levels of fever from two groups presented to the emergency department. One group was admitted for FS (n = 213) and the other for GE (n = 220). In the FS group, the etiology of fever was respiratory tract infection (74.2%), otitis media (7%), GE (7%), tonsillitis (4.2%), scarlet fever (2.3%) chickenpox (1.4%), urinary tract infection (1.4%), postvaccination reaction (0.9%), or unidentified (1.4%). In all patients, capillary pH and blood Pco(2) were measured immediately on admission to the hospital. KEY FINDINGS: Respiratory alkalosis was found in children with FS (pH 7.46 ± 0.04, [mean ± standard deviation] Pco(2) 29.5 ± 5.5 mmHg), whereas a metabolic acidosis was seen in all children admitted for GE (pH 7.31 ± 0.03, Pco(2) 37.7 ± 4.3 mmHg; p < 0.001 for both parameters). No FS were observed in the latter group. A subgroup (n = 15; 7%) of the patients with FS had GE and, notably, their blood pH was more alkaline (pH 7.44 ± 0.04) than in the GE-admitted group. During the enrollment period, eight of the patients were admitted on separate occasions because of FS or GE. Consistent with the view that generation of FS requires a genetic susceptibility in addition to acute seizure triggering factors, each of these patients had an alkalotic blood pH when admitted because of FS, whereas they had an acidotic pH (and no FS) when admitted because of GE (pH 7.47 ± 0.05 vs. pH 7.33 ± 0.03, p < 0.005). SIGNIFICANCE: The results show that FS are associated with a systemic respiratory alkalosis, irrespective of the severity of the underlying infection as indicated by the level of fever. The lack of FS in GE patients is attributable to low pH, which also explains the fact that children with a susceptibility to FS do not have seizures when they have GE-induced fever that is associated with acidosis. The present demonstration of a close link between FS and respiratory alkalosis may pave the way for further clinical studies and attempts to design novel therapies for the treatment of FS by controlling the systemic acid-base status.

Sleep disturbances in patients admitted to a step-down unit after ICU discharge: the role of mechanical ventilation.

BACKGROUND: Severe sleep disruption is a well-documented problem in mechanically ventilated, critically ill patients during their time in the intensive care unit (ICU), but little attention has been paid to the period when these patients become clinically stable and are transferred to a step-down unit (SDU). We monitored the 24-h sleep pattern in 2 groups of patients, one on mechanical ventilation and the other breathing spontaneously, admitted to our SDU to assess the presence of sleep abnormalities and their association with mechanical ventilation. METHODS: Twenty-two patients admitted to an SDU underwent 24-h polysomnography with monitoring of noise and light. RESULTS: One patient did not complete the study. At night, 10 patients showed reduced sleep efficiency, 6 had reduced percentage of REM sleep, and 3 had reduced percentage of slow wave sleep (SWS). Sleep amount and quality did not differ between patients breathing spontaneously and those on mechanical ventilation. Clinical severity (SAPS(II) score) was significantly correlated with daytime total sleep time and efficiency (r = 0.51 and 0.5, P < 0.05, respectively); higher pH was correlated with reduced sleep quantity and quality; and higher PaO(2) was correlated with increased SWS (r = 0.49; P = 0.02). CONCLUSIONS: Patients admitted to an SDU after discharge from an ICU still have a wide range of sleep abnormalities. These abnormalities are mainly associated with a high severity score and alkalosis. Mechanical ventilation does not appear to be a primary cause of sleep impairment.

A mathematical model of tumour and blood pHe regulation: The HCO3-/CO2 buffering system.

Malignant tumours are characterised by a low, acidic extracellular pH (pHe) which facilitates invasion and metastasis. Previous research has proposed the potential benefits of manipulating systemic pHe, and recent experiments have highlighted the potential for buffer therapy to raise tumour pHe, prevent metastases, and prolong survival in laboratory mice. To examine the physiological regulation of tumour buffering and investigate how perturbations of the buffering system (via metabolic/respiratory disorders or changes in parameters) can alter tumour and blood pHe, we develop a simple compartmentalised ordinary differential equation model of pHe regulation by the HCO3-/CO2 buffering system. An approximate analytical solution is constructed and used to carry out a sensitivity analysis, where we identify key parameters that regulate tumour pHe in both humans and mice. From this analysis, we suggest promising alternative and combination therapies, and identify specific patient groups which may show an enhanced response to buffer therapy. In addition, numerical simulations are performed, validating the model against well-known metabolic/respiratory disorders and predicting how these disorders could change tumour pHe.

Medication-induced hypophosphatemia: a review.

Hypophosphatemia (serum phosphorus concentration <2.5 mg/dl, 0.8 mmol/l), although rare in the general population, is commonly observed in hospitalized patients and may be associated with drug therapy. In fact, hypophosphatemia frequently develops in the course of treatment with drugs used in every-day clinical practice including diuretics and bisphosphonates. Proper diagnostic approach of patients with low serum phosphorus concentrations should involve a detailed medical history with special attention to the recent use of medications. The clinical manifestations of drug-induced hypophosphatemia are usually mild but might also be severe and potentially life-threatening. This review aims at a thorough understanding of the underlying pathophysiological mechanisms and risk factors of drug therapy-related hypophosphatemia thus allowing prevention and effective intervention strategies.

Arterial base deficit in pulmonary embolism is an index of severity and diagnostic delay.

In acute pulmonary embolism, patients free from circulatory failure usually present a blood gas pattern consistent with respiratory alkalosis. We investigated whether the appearance of arterial base deficit in these patients indicates disease severity and diagnostic delay. Twenty-four consecutive patients with pulmonary embolism were retrospectively evaluated. Twelve patients had arterial base excess > or =0 mmol/L (Group 1), and 12 patients arterial base deficit <0 mmol/L (Group 2). No patient showed signs of circulatory failure. Group 1 was characterized by a mean base excess of 2.2 +/- 1.7 mmol/L, while in Group 2, the mean base deficit was -1.9 +/- 0.7 mmol/L (p < 0.0001). At 1 week since the embolism, 11 patients of Group 1 and 6 of Group 2 received a PE diagnosis (p < 0.05). The vascular obstruction index was more severe in Group 2 than in Group 1 (48 +/- 12 vs. 36 +/- 17%, respectively, p < 0.05). In Group 2, the PaCO(2) was lower (33 +/- 3 vs. 36 +/- 5 mmHg, respectively, p < 0.05), the arterial pH was decreased (7.442 +/- 0.035 vs. 7.472 +/- 0.050, respectively, p = 0.097), the Pv(50) was lower (28.3 +/- 1.7 vs. 29.8 +/- 1.6 mmHg, respectively, p < 0.05), the aHCO(3) (-) was lower (22.5 +/- 0.7 vs. 26.1 +/- 1.6 mmol/L, respectively; p < 0.0001), while between the Groups, O(2) delivery, O(2) mixed venous saturation, and O(2) extraction ratio were equivalent. Despite no signs of circulatory failure, an arterial Base deficit develops in patients with respiratory alkalosis subsequent to more severe pulmonary vascular obstruction. Diagnostic delay favors a base deficit. Depending on the degree of hypocapnia, there may be limitation of peripheral O(2) uptake despite adequate O(2) availability. Progressive bicarbonate deficit suggests an increased risk for underlying conditions such as cardio-respiratory disorders or cancer, and requires close control and treatment.

Neurobiological and physiological mechanisms of fever-related epileptiform syndromes.

Febrile seizures (FS) are the most common type of convulsive events in children. FS have been extensively studied using animal models, where rat and mice pups are placed in a hyperthermic environment. Such work has largely focused on the consequences rather than on the mechanisms of experimental febrile seizures (eFS). We have recently shown that eFS are preceded by a dramatic rise in the rate of respiration. The consequent respiratory alkalosis affecting the brain and increasing neuronal excitability is a direct cause of the eFS [1]. If a similar mechanism contributes to human FS and other fever-related epileptiform syndromes, a number of factors operating at the molecular, cellular and systems level that have not been previously thought to be involved in their etiology must be considered. These include physiological and pathophysiological factors affecting CO(2) chemosensitivity as well as cellular and systemic mechanisms of acid-base regulation. Furthermore, a critical role for brain pH in FS points to novel types of susceptibility genes, which include genes coding pH-sensitive target proteins (e.g. neuronal ion channels) and pH-regulatory proteins. We will discuss these novel ideas and putative therapies based on them.

Brainstem infarct presenting as torsades de pointes.

Hypokalemia, as an adverse consequence of severe alkalosis, can prolong QT interval and cause torsades de pointes. This report describes a rare case of central neurogenic hyperventilation as a result of brainstem infarct, presenting primarily with refractory ventricular tachyarrhythmia due to secondary hypokalemia.