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The European Respiratory Journal Jun 2022Pulmonary arterial hypertension (PAH) is a rare dyspnoea-fatigue syndrome caused by a progressive increase in pulmonary vascular resistance and eventual right... (Review)
Review
Pulmonary arterial hypertension (PAH) is a rare dyspnoea-fatigue syndrome caused by a progressive increase in pulmonary vascular resistance and eventual right ventricular (RV) failure. In spite of extensive pulmonary vascular remodelling, lung function in PAH is generally well preserved, with hyperventilation and increased physiological dead space, but minimal changes in lung mechanics and only mild to moderate hypoxaemia and hypocapnia. Hypoxaemia is mainly caused by a low mixed venous oxygen tension from a decreased cardiac output. Hypocapnia is mainly caused by an increased chemosensitivity. Exercise limitation in PAH is cardiovascular rather than ventilatory or muscular. The extent of pulmonary vascular disease in PAH is defined by multipoint pulmonary vascular pressure-flow relationships with a correction for haematocrit. Pulsatile pulmonary vascular pressure-flow relationships in PAH allow for the assessment of RV hydraulic load. This analysis is possible either in the frequency domain or in the time domain. The RV in PAH adapts to increased afterload by an increased contractility to preserve its coupling to the pulmonary circulation. When this homeometric mechanism is exhausted, the RV dilates to preserve flow output by an additional heterometric mechanism. Right heart failure is then diagnosed by imaging of increased right heart dimensions and clinical systemic congestion signs and symptoms. The coupling of the RV to the pulmonary circulation is assessed by the ratio of end-systolic to arterial elastances, but these measurements are difficult. Simplified estimates of RV-pulmonary artery coupling can be obtained by magnetic resonance or echocardiographic imaging of ejection fraction.
Topics: Familial Primary Pulmonary Hypertension; Heart Failure; Humans; Hypertension, Pulmonary; Hypocapnia; Hypoxia; Pulmonary Arterial Hypertension; Pulmonary Artery; Ventricular Dysfunction, Right; Ventricular Function, Right
PubMed: 34737219
DOI: 10.1183/13993003.02334-2021 -
Sleep Mar 2023Central sleep apnea is not a single disorder; it can present as an isolated disorder or as a part of other clinical syndromes. In some conditions, such as heart failure,... (Review)
Review
Central sleep apnea is not a single disorder; it can present as an isolated disorder or as a part of other clinical syndromes. In some conditions, such as heart failure, central apneic events are due to transient inhibition of ventilatory motor output during sleep, owing to the overlapping influences of sleep and hypocapnia. Specifically, the sleep state is associated with removal of wakefulness drive to breathe; thus, rendering ventilatory motor output dependent on the metabolic ventilatory control system, principally PaCO2. Accordingly, central apnea occurs when PaCO2 is reduced below the "apneic threshold". Our understanding of the pathophysiology of central sleep apnea has evolved appreciably over the past decade; accordingly, in disorders such as heart failure, central apnea is viewed as a form of breathing instability, manifesting as recurrent cycles of apnea/hypopnea, alternating with hyperpnea. In other words, ventilatory control operates as a negative-feedback closed-loop system to maintain homeostasis of blood gas tensions within a relatively narrow physiologic range, principally PaCO2. Therefore, many authors have adopted the engineering concept of "loop gain" (LG) as a measure of ventilatory instability and susceptibility to central apnea. Increased LG promotes breathing instabilities in a number of medical disorders. In some other conditions, such as with use of opioids, central apnea occurs due to inhibition of rhythm generation within the brainstem. This review will address the pathogenesis, pathophysiologic classification, and the multitude of clinical conditions that are associated with central apnea, and highlight areas of uncertainty.
Topics: Humans; Sleep Apnea, Central; Hypocapnia; Respiration; Sleep; Heart Failure
PubMed: 35551411
DOI: 10.1093/sleep/zsac113 -
Archivos Argentinos de Pediatria Oct 2020Cerebral edema (CE) is the most severe complication of diabetic ketoacidosis (DKA) in children. There is no accurate knowledge of CE pathogenesis and its onset has been...
INTRODUCTION
Cerebral edema (CE) is the most severe complication of diabetic ketoacidosis (DKA) in children. There is no accurate knowledge of CE pathogenesis and its onset has been related to intravenous rehydration therapy during the initial treatment.
OBJECTIVES
To estimate the prevalence of CE among DKA patients treated at Hospital General de Niños Pedro de Elizalde with intravenous rehydration and analyze potential risk factors for the development of CE.
MATERIALS AND METHODS
Cross-sectional prevalence study and exploratory analysis to compare clinical and laboratory characteristics between patients with and without CE. Patients aged 1-18 years hospitalized with the diagnosis of DKA between January 1st, 2005 and December 31st, 2014 were included.
RESULTS
A total of 693 DKA events from 561 medical records were analyzed. Ten patients had evidence of CE (1.44 %; 95 % confidence interval: 0.8-2.6). Patients with CE had higher serum urea levels (p < 0.001), lower carbon dioxide pressure (p < 0.001), and lower serum sodium levels (p < 0.001) than those without CE.
CONCLUSION
The prevalence of CE among DKA patients was 1.44 %, smaller than that reported in our country (1.8 %). The risk factors at admission associated with CE development were high serum urea levels, hyponatremia, and hypocapnia.
Topics: Adolescent; Argentina; Brain Edema; Child; Child, Preschool; Cross-Sectional Studies; Diabetic Ketoacidosis; Female; Fluid Therapy; Humans; Hypocapnia; Hyponatremia; Infant; Male; Prevalence; Risk Factors; Urea
PubMed: 32924396
DOI: 10.5546/aap.2020.eng.332 -
British Journal of Anaesthesia Feb 2023Previous studies indicated an association between impaired cerebral perfusion and post-procedural neurological disorders. We investigated whether intra-procedural...
BACKGROUND
Previous studies indicated an association between impaired cerebral perfusion and post-procedural neurological disorders. We investigated whether intra-procedural hypoxaemia or hypocapnia are associated with delirium after surgery.
METHODS
Inpatients ≥60 yr of age undergoing anaesthesia for surgical or interventional procedures between 2009 and 2020 at an academic healthcare network in the USA (Massachusetts) were included in this hospital registry study. The primary exposure was intra-procedural hypoxaemia, defined as peripheral oxygen saturation <90% for >2 cohering min. The co-primary exposure was hypocapnia during general anaesthesia, defined as end-tidal carbon dioxide pressure ≤25 mm Hg for >5 cohering min. The primary outcome was delirium within 7 days after surgery.
RESULTS
Of 71 717 included patients, 1702 (2.4%) developed postoperative delirium, and hypoxaemia was detected in 2532 (3.5%). Of 42 894 patients undergoing general anaesthesia, 532 (1.2%) experienced hypocapnia. The occurrence of either hypoxaemia (adjusted odds ratio [OR]=1.71; 95% confidence interval [CI], 1.40-2.07; P<0.001) or hypocapnia (OR=1.77; 95% CI, 1.30-2.41; P<0.001) was associated with a higher risk of delirium within 7 days. Both associations were dependent on the magnitude, and increased with event duration (OR=1.03; 95% CI, 1.02-1.04; P<0.001 and OR=1.01; 95% CI, 1.00-1.01; P=0.005, for each minute increase in the longest continuous episode, respectively). There was no association between occurrence of hypercapnia and postoperative delirium (OR=1.24; 95% CI, 0.90-1.71; P=0.181).
CONCLUSIONS
Intra-procedural hypoxaemia and hypocapnia were dose-dependently associated with a higher risk of postoperative delirium. These findings support maintaining normal gas exchange to avoid postoperative neurological disorders.
Topics: Humans; Aged; Emergence Delirium; Hypocapnia; Postoperative Complications; Hypoxia; Nervous System Diseases
PubMed: 36192221
DOI: 10.1016/j.bja.2022.08.032 -
The Cochrane Database of Systematic... Dec 2019High intracranial pressure (ICP) is the most frequent cause of death and disability after severe traumatic brain injury (TBI). It is usually treated with general... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High intracranial pressure (ICP) is the most frequent cause of death and disability after severe traumatic brain injury (TBI). It is usually treated with general maneuvers (normothermia, sedation, etc.) and a set of first-line therapeutic measures (moderate hypocapnia, mannitol, etc.). When these measures fail, second-line therapies are initiated, which include: barbiturates, hyperventilation, moderate hypothermia, or removal of a variable amount of skull bone (secondary decompressive craniectomy).
OBJECTIVES
To assess the effects of secondary decompressive craniectomy (DC) on outcomes of patients with severe TBI in whom conventional medical therapeutic measures have failed to control raised ICP.
SEARCH METHODS
The most recent search was run on 8 December 2019. We searched the Cochrane Injuries Group's Specialised Register, CENTRAL (Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP) and ISI Web of Science (SCI-EXPANDED & CPCI-S). We also searched trials registries and contacted experts.
SELECTION CRITERIA
We included randomized studies assessing patients over the age of 12 months with severe TBI who either underwent DC to control ICP refractory to conventional medical treatments or received standard care.
DATA COLLECTION AND ANALYSIS
We selected potentially relevant studies from the search results, and obtained study reports. Two review authors independently extracted data from included studies and assessed risk of bias. We used a random-effects model for meta-analysis. We rated the quality of the evidence according to the GRADE approach.
MAIN RESULTS
We included three trials (590 participants). One single-site trial included 27 children; another multicenter trial (three countries) recruited 155 adults, the third trial was conducted in 24 countries, and recruited 408 adolescents and adults. Each study compared DC combined with standard care (this could include induced barbiturate coma or cooling of the brain, or both). All trials measured outcomes up to six months after injury; one also measured outcomes at 12 and 24 months (the latter data remain unpublished). All trials were at a high risk of bias for the criterion of performance bias, as neither participants nor personnel could be blinded to these interventions. The pediatric trial was at a high risk of selection bias and stopped early; another trial was at risk of bias because of atypical inclusion criteria and a change to the primary outcome after it had started. Mortality: pooled results for three studies provided moderate quality evidence that risk of death at six months was slightly reduced with DC (RR 0.66, 95% CI 0.43 to 1.01; 3 studies, 571 participants; I = 38%; moderate-quality evidence), and one study also showed a clear reduction in risk of death at 12 months (RR 0.59, 95% CI 0.45 to 0.76; 1 study, 373 participants; high-quality evidence). Neurological outcome: conscious of controversy around the traditional dichotomization of the Glasgow Outcome Scale (GOS) scale, we chose to present results in three ways, in order to contextualize factors relevant to clinical/patient decision-making. First, we present results of death in combination with vegetative status, versus other outcomes. Two studies reported results at six months for 544 participants. One employed a lower ICP threshold than the other studies, and showed an increase in the risk of death/vegetative state for the DC group. The other study used a more conventional ICP threshold, and results favoured the DC group (15.7% absolute risk reduction (ARR) (95% CI 6% to 25%). The number needed to treat for one beneficial outcome (NNTB) (i.e. to avoid death or vegetative status) was seven. The pooled result for DC compared with standard care showed no clear benefit for either group (RR 0.99, 95% CI 0.46 to 2.13; 2 studies, 544 participants; I = 86%; low-quality evidence). One study reported data for this outcome at 12 months, when the risk for death or vegetative state was clearly reduced by DC compared with medical treatment (RR 0.68, 95% CI 0.54 to 0.86; 1 study, 373 participants; high-quality evidence). Second, we assessed the risk of an 'unfavorable outcome' evaluated on a non-traditional dichotomized GOS-Extended scale (GOS-E), that is, grouping the category 'upper severe disability' into the 'good outcome' grouping. Data were available for two studies (n = 571). Pooling indicated little difference between DC and standard care regarding the risk of an unfavorable outcome at six months following injury (RR 1.06, 95% CI 0.69 to 1.63; 544 participants); heterogeneity was high, with an I value of 82%. One trial reported data at 12 months and indicated a clear benefit of DC (RR 0.81, 95% CI 0.69 to 0.95; 373 participants). Third, we assessed the risk of an 'unfavorable outcome' using the (traditional) dichotomized GOS/GOS-E cutoff into 'favorable' versus 'unfavorable' results. There was little difference between DC and standard care at six months (RR 1.00, 95% CI 0.71 to 1.40; 3 studies, 571 participants; low-quality evidence), and heterogeneity was high (I = 78%). At 12 months one trial suggested a similar finding (RR 0.95, 95% CI 0.83 to 1.09; 1 study, 373 participants; high-quality evidence). With regard to ICP reduction, pooled results for two studies provided moderate quality evidence that DC was superior to standard care for reducing ICP within 48 hours (MD -4.66 mmHg, 95% CI -6.86 to -2.45; 2 studies, 182 participants; I = 0%). Data from the third study were consistent with these, but could not be pooled. Data on adverse events are difficult to interpret, as mortality and complications are high, and it can be difficult to distinguish between treatment-related adverse events and the natural evolution of the condition. In general, there was low-quality evidence that surgical patients experienced a higher risk of adverse events.
AUTHORS' CONCLUSIONS
Decompressive craniectomy holds promise of reduced mortality, but the effects of long-term neurological outcome remain controversial, and involve an examination of the priorities of participants and their families. Future research should focus on identifying clinical and neuroimaging characteristics to identify those patients who would survive with an acceptable quality of life; the best timing for DC; the most appropriate surgical techniques; and whether some synergistic treatments used with DC might improve patient outcomes.
Topics: Brain Injuries, Traumatic; Decompressive Craniectomy; Humans; Intracranial Hypertension; Intracranial Pressure; Randomized Controlled Trials as Topic
PubMed: 31887790
DOI: 10.1002/14651858.CD003983.pub3 -
Journal of the American College of... Sep 2021Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medically unexplained illness characterized by severe fatigue limiting normal daily activities for at... (Review)
Review
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medically unexplained illness characterized by severe fatigue limiting normal daily activities for at least 6 months accompanied by problems with unrefreshing sleep, exacerbation of symptoms following physical or mental efforts (postexertional malaise [PEM]), and either cognitive reports or physiological evidence of orthostatic intolerance in the form of either orthostatic tachycardia and/or hypocapnia. Although rarely considered to have cardiac dysfunction, ME/CFS patients frequently have reduced stroke volume with a significant inverse relation between cardiac output and PEM severity. Magnetic resonance imaging of ME/CFS patients compared with normal control subjects found significantly reduced stroke, end-systolic, and end-diastolic volumes together with reduced end-diastolic wall mass. Another cardiovascular abnormality is reduced nocturnal blood pressure assessed by 24-hour monitoring. Autonomic dysfunction is also frequently observed with postural orthostatic tachycardia and/or hypocapnia. Two consecutive cardiopulmonary stress tests may provide metabolic data substantiating PEM.
Topics: Blood Pressure; Blood Volume; Cardiovascular Diseases; Fatigue Syndrome, Chronic; Humans; Orthostatic Intolerance; Stroke Volume
PubMed: 34474739
DOI: 10.1016/j.jacc.2021.06.045 -
Pediatric Research Apr 2022There is no consensus on the optimal pCO levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates.... (Review)
Review
There is no consensus on the optimal pCO levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates. A systematic review was conducted in accordance with the PRISMA statement and MOOSE guidelines. Two hundred and ninety-nine studies were screened and 37 studies included. Covidence online software was employed to streamline relevant articles. Hypocapnia was associated with predominantly neurological side effects while hypercapnia was linked with neurological, respiratory and gastrointestinal outcomes and Retinpathy of prematurity (ROP). Permissive hypercapnia did not decrease periventricular leukomalacia (PVL), ROP, hydrocephalus or air leaks. As safe pCO ranges were not explicitly concluded in the studies chosen, it was indirectly extrapolated with reference to pCO levels that were found to increase the risk of neonatal disease. Although PaCO ranges were reported from 2.6 to 8.7 kPa (19.5-64.3 mmHg) in both term and preterm infants, there are little data on the safety of these ranges. For permissive hypercapnia, parameters described for bronchopulmonary dysplasia (BPD; PaCO 6.0-7.3 kPa: 45.0-54.8 mmHg) and congenital diaphragmatic hernia (CDH; PaCO ≤ 8.7 kPa: ≤65.3 mmHg) were identified. Contradictory findings on the effectiveness of permissive hypercapnia highlight the need for further data on appropriate CO parameters and correlation with outcomes. IMPACT: There is no consensus on the optimal pCO levels in the newborn. There is no consensus on the effectiveness of permissive hypercapnia in neonates. A safe range of pCO of 5-7 kPa was inferred following systematic review.
Topics: Carbon Dioxide; Humans; Hypercapnia; Hypocapnia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Respiration, Artificial
PubMed: 34230621
DOI: 10.1038/s41390-021-01473-y -
Journal of Applied Physiology... Jan 2023
PubMed: 36592407
DOI: 10.1152/japplphysiol.00699.2022 -
Medical Gas Research 2020Carbon dioxide is a common gas in the air which has been widely used in medical treatment. A carbon dioxide molecule consists of two oxygen atoms and one carbon atom... (Review)
Review
Carbon dioxide is a common gas in the air which has been widely used in medical treatment. A carbon dioxide molecule consists of two oxygen atoms and one carbon atom through a covalent bond. In the body, carbon dioxide reacts with water to produce carbonic acid. In healthy people, carbon dioxide is maintained within a narrow range (35-45 mmHg) by physiological mechanisms. The role of hypocapnia (partial pressure of carbon dioxide < 35 mmHg) and hypercapnia (partial pressure of carbon dioxide > 45 mmHg) in the nervous system is intricate. Past researches mainly focus on the effect of hypocapnia to nerve protection. Nevertheless, Hypercapnia seems to play an important role in neuroprotection. The mechanisms of hypocapnia and hypercapnia in the nervous system deserve our attention. The purpose of this review is to summarize the effect of hypocapnia and hypercapnia in stroke and traumatic brain injury.
Topics: Animals; Brain Injuries; Carbon Dioxide; Humans; Stroke
PubMed: 32541133
DOI: 10.4103/2045-9912.285561