Hypocapnia is an independent predictor of in-hospital mortality in acute heart failure.

AIMS: Acute heart failure (AHF) poses a major threat to hospitalized patients for its high mortality rate and serious complications. The aim of this study is to determine whether hypocapnia [defined as the partial pressure of arterial carbon dioxide (PaCO2 ) below 35 mmHg] on admission could be associated with in-hospital all-cause mortality in AHF. METHODS AND RESULTS: A total of 676 patients treated in the coronary care unit for AHF were retrospectively analysed, and the study endpoint was in-hospital all-cause mortality. The 1:1 propensity score matching (PSM) analysis, Kaplan-Meier curve, and Cox regression model were used to explore the association between hypocapnia and in-hospital all-cause mortality in AHF. Receiver operating characteristic (ROC) curve and Delong's test were used to assess the performance of hypocapnia in predicting in-hospital all-cause mortality in AHF. The study cohort included 464 (68.6%) males and 212 (31.4%) females, and the median age was 66 years (interquartile range 56-74 years). Ninety-eight (14.5%) patients died during hospitalization and presented more hypocapnia than survivors (76.5% vs. 45.5%, P < 0.001). A 1:1 PSM was performed between hypocapnic and non-hypocapnic patients, with 264 individuals in each of the two groups after matching. Compared with non-hypocapnic patients, in-hospital mortality was significantly higher in hypocapnic patients both before (22.2% vs. 6.8%, P < 0.001) and after (20.8% vs. 8.7%, P < 0.001) PSM. Kaplan-Meier curve showed a significantly higher probability of in-hospital death in patients with hypocapnia before and after PSM (both P < 0.001 for the log-rank test). Multivariate Cox regression analysis showed that hypocapnia was an independent predictor of AHF mortality both before [hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.23-3.98; P = 0.008] and after (HR 2.19; 95% CI 1.18-4.07; P = 0.013) PSM. Delong's test showed that the area under the ROC curve was improved after adding hypocapnia into the model (0.872, 95% CI 0.839-0.901 vs. 0.855, 95% CI 0.820-0.886, P = 0.028). PaCO2 was correlated with the estimated glomerular filtration rate (r = 0.20, P = 0.001), left ventricular ejection fraction (r = 0.13, P < 0.001), B-type natriuretic peptide (r = -0.28, P < 0.001), and lactate (r = -0.15, P < 0.001). Kaplan-Meier curve of PaCO2 tertiles and multivariate Cox regression analysis showed that the lowest PaCO2 tertile was associated with increased risk of in-hospital mortality in AHF (all P < 0.05). CONCLUSIONS: Hypocapnia is an independent predictor of in-hospital mortality for AHF.

The Effect of Mild Hypocapnia on Postoperative Ecchymosis in Rhinoplasty.

PURPOSE: Ecchymosis and edema are the most common complications in patients following rhinoplasty in the early postoperative period. Vasoconstriction created by hypocarbia may have a positive effect on postoperative ecchymosis. The aim of this study was to evaluate the effect of mild hypocapnia induced in rhinoplasty on the severity of periorbital ecchymosis. METHODS: The study was carried out retrospectively in the digital photographs (control group and study group) of 31 participants who underwent open technical rhinoplasty between January and March 2019. During the operation, partial carbon dioxide pressure in the study group was kept in the range of 32 to 38 mmHg and in the control group between 42 and 46 mmHg and this was confirmed by arterial blood gas measurements taken during the operation. Measuring the brightness and shadows of digital photos Digital color meter was used in MacOS X as a computer software. RESULTS: The mean ratio of periorbital ecchymosis to forehead brightness was 0.84 ± 0.05 in the study group and 0.81 ± 0.03 in the control group. There was no significant difference between the study and control groups (P > .05). CONCLUSION: This study investigates the potential role of hypocapnia on postoperative ecchymosis during rhinoplasty. The severity of ecchymosis was less in the patients with induced mild hypocapnia regarding both subjective and objective evaluations, but this difference didn't reach statistical significance compared to the normocapnic control group.

Central sleep apnea: pathophysiologic classification.

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.

Clinical determinants and prognostic significance of hypocapnia in acute heart failure.

The aim of this research was to examine the prevalence of hyperventilation (defined by pCO2 value) among acute heart failure (AHF) patients and to link it with potential triggers and prognosis. All patients underwent dyspnea severity assessment and capillary blood examination on hospital admission and during hospitalization. Out of 241 AHF patients, 57(24%) were assigned to low pCO2 group (pCO2 ≤ 30 mmHg) and 184 (76%) to normal pCO2 group (pCO2 > 30 mmHg). Low pCO2 group had significantly lower HCO3- (22.3 ± 3.4 vs 24.7 ± 2.9 mmol/L, p < 0.0001) and significantly higher lactate level (2.53 ± 1.6 vs 2.14 ± 0.97 mmol/L, p = 0.03). No differences between groups were observed in respect to the following potential triggers of hyperventilation: hypoxia (sO2 92.5 ± 5.2 vs 92 ± 5.6% p = 0.57), infection (CRP 10.5[4.9-26.4]vs 7.15[3.45-17.35] mg/L, p = 0.47), dyspnea severity (7.8 ± 2.3vs 8.0 ± 2.3 points, p = 0.59) and pulmonary congestion (82.5 vs 89.1%, p = 0.19), respectively. Low pCO2 value was related to an increased 4-year all-cause mortality hazard ratio (HR) (95% CI) 2.2 (1.3-3.6); p = 0.002 and risk of death and of rehospitalization for HF, HR (95% CI) 2.0 (1.3-3.0); p = 0.002. Hyperventilation is relatively frequent in AHF and is related to poor prognosis. Low pCO2 was not contingent on expected potential triggers of dyspnea but rather on tissue hypoperfusion.

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.

Hypocapnia in early hours of life is associated with brain injury in moderate to severe neonatal encephalopathy.

OBJECTIVE: To evaluate the association between hypocapnia within the first 24 h of life and brain injury assessed by a detailed MRI scoring system in infants receiving therapeutic hypothermia (TH) for neonatal encephalopathy (NE) stratified by the stage of NE. STUDY DESIGN: This retrospective cohort study included infants who received TH for mild to severe NE. RESULTS: 188 infants were included in the study with 48% having mild and 52% moderate-severe NE. Infants with moderate-severe NE spent more time in hypocapnia (PCO2 ≤ 35 mmHg) and presented with more severe brain injury on MRI compared to mild cases. The MRI injury score increased by 6% for each extra hour spent in hypocapnic range in infants with moderate-severe NE. There was no association between hypocapnia and injury scores in mild cases. CONCLUSION: In infants with moderate-severe NE, the hours spent in hypocapnia was an independent predictor of brain injury.

The physiological basis of pulmonary arterial hypertension.

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.

Impact of intraoperative hypocapnia on postoperative complications in laparoscopic surgery for colorectal cancer.

PURPOSE: In laparoscopic surgery (LS) for colorectal cancer (CRC), the relationship between intraoperative end-tidal carbon dioxide concentration (EtCO2) and surgery-related complications remains unexplored. This study assessed the impact of intraoperative EtCO2 on postoperative complications in LS for CRC. METHODS: In total, 909 patients who underwent LS for CRC were enrolled. Hypocapnia and hypercapnia were defined as EtCO2 < 35 mmHg and > 40 mmHg, respectively, and the relationships between hypocapnia or hypercapnia duration and postoperative complications were analyzed. RESULTS: The median (range) durations of hypocapnia and hypercapnia were 2.0 (0-8.3) h and 0.3 (0-5.8) h, respectively. Complications were observed in 208 cases (23.0%), which included 37 (4.1%) instances of anastomotic leakage and 86 (9.5%) of superficial surgical site infection (SSI). While the hypercapnia duration was not associated with the short-term outcomes, prolonged hypocapnia was significantly correlated with complications (p = 0.02), specifically superficial SSI (p = 0.005). Multivariate analyses adjusted for confounding factors confirmed that hypocapnia prolongation was an independent risk factor for postoperative superficial SSI [OR 1.19; 95% confidence interval (Cl) 1.03-1.36, p = 0.01]. CONCLUSION: Intraoperative hypocapnia may be a risk factor for postoperative complications, in particular superficial SSI, in LS for CRC.

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.

Hypotension and Hypocapnia During General Anesthesia in Piglets: Study of S100b as an Acute Biomarker for Cerebral Tissue Injury.

BACKGROUND: Hypotension and/or hypocapnia might increase general anesthesia (GA)-related neuromorbidity in infants, but safe levels of perioperative blood pressure are poorly defined. Serum protein S100b has been used as screening, monitoring, and prediction tool in the management of patients with traumatic brain injury. Using an animal model, we investigated serum S100b as an acute biomarker of cerebral hypoperfusion and cerebral cell dysfunction during hypotension, hypocapnia, or combined hypotension/hypocapnia during GA. METHODS: Fifty-seven sevoflurane-midazolam anesthetized piglets aged 4 to 6 weeks were randomly allocated to control (n=9), hypotension (n=18), hypocapnia (n=20), or combined hypotension and hypocapnia (n=10). Hypotension (target mean arterial blood pressure: 35 to 38 or 27 to 30 mm Hg) was induced by blood withdrawal and nitroprusside infusion, and hypocapnia by hyperventilation (target PaCO2: 28 to 30 and 23 to 25 mm Hg). Serum S100b and albumin were measured at baseline, before and 60 minutes after the interventions, and following 60-minute recovery. RESULTS: Serum S100b concentrations decreased over time (P=0.001), but there was no difference in S100b between control piglets and those exposed to hypotension, hypocapnea, or a combination of the both (P=0.105). Albumin decreased in all 4 groups (P=0.001). CONCLUSION: S100b did not increase following 60 minutes of systemic hypotension and/or hypocapnia during GA in piglets. In this setting, the use of S100b as a biomarker of cerebral cell tissue dysfunction cannot be supported.

Do acute stroke patients develop hypocapnia? A systematic review and meta-analysis.

PURPOSE: Carbon dioxide (CO2) is a potent cerebral vasomotor agent. Despite reduction in CO2 levels (hypocapnia) being described in several acute diseases, there is no clear data on baseline CO2 values in acute stroke. The aim of the study was to systematically assess CO2 levels in acute stroke. MATERIAL AND METHODS: Four online databases, Web of Science, MEDLINE, EMBASE and CENTRAL, were searched for articles that described either partial pressure of arterial CO2 (PaCO2) and end-tidal CO2 (EtCO2) in acute stroke. RESULTS: After screening, based on predefined inclusion and exclusion criteria, 20 studies were retained. There were 5 studies in intracerebral hemorrhage and 15 in ischemic stroke, totalling 660 stroke participants. Acute stroke was associated with a significant decrease in CO2 levels compared to controls. Cerebral haemodynamic studies using transcranial Doppler ultrasonography demonstrated a significant reduction in cerebral blood flow velocities and cerebral autoregulation in acute stroke patients. CONCLUSION: The evidence from this review suggests that acute stroke patients are significantly more likely than controls to be hypocapnic, supporting the value of routine CO2 assessment in the acute stroke setting. Further studies are required in order to evaluate the clinical impact of these findings.

Association between hypocapnia and ventilation during the first days of life and brain injury in asphyxiated newborns treated with hypothermia.

PURPOSE: Therapeutic hypothermia is the standard treatment for asphyxiated newborns. Since hypocapnia is common in these newborns, the aim of this study was to assess the association among hypocapnia, ventilation, and brain injury. METHODS: We conducted a retrospective cohort study of all asphyxiated newborns treated with hypothermia from 2008 to 2014. Partial pressure of carbon dioxide (pCO2), ventilatory status, and modes of ventilation were recorded during the first 4 days of life. Brain injury was evaluated using brain magnetic resonance imaging. Differences between intubated and nonintubated newborns and between the newborns who developed brain injury or not were assessed. RESULTS: One hundred ninety-eight asphyxiated newborns were treated with hypothermia. During the first 2 days of life, intubated newborns had consistently lower pCO2 levels (respectively, 29.01 ± 8.55, p < .001 on day 1 of life and 33.65 ± 7.12, p = .004 on day 2 of life). Fifty-nine percent of the intubated newborns developed brain injury versus only 43% of the nonintubated newborns (p = .046). The lowest pCO2 levels averaged over the first 4 days of life were significantly decreased in newborns developing brain injury (p = .02) and significantly associated with brain injury severity (p = .01). After adjusting for potential cofounders, the lowest pCO2 averaged over days 1-4 of life remained significantly associated with an increased risk of brain injury (odds ratio [95%CI]: 1.07 [1.00-1.14]; p = .04). CONCLUSIONS: Intubated and ventilated asphyxiated newborns experienced more severe hypocapnia, and had higher incidences of brain injury. Hypocapnia during the first 4 days of life was associated with an increased risk of developing (more severe) brain injury.

Different strategies to initiate and maintain hyperventilation: their effect on continuous estimates of dynamic cerebral autoregulation.

OBJECTIVE: Capnography is a key monitoring intervention in several neurologically vulnerable clinical states. Cerebral autoregulation (CA) describes the ability of the cerebrovascular system to maintain a near constant cerebral blood flow throughout fluctuations in systemic arterial blood pressure, with the partial pressure of arterial carbon dioxide known to directly influence CA. Previous work has demonstrated dysautoregulation lasting around 30 s prior to the anticipated augmentation of hyperventilation-associated hypocapnia. In order assess to potential benefit of hypocapnic interventions in an acute stroke setting, minimisation of dysregulation is paramount. APPROACH: Hyperventilation strategies to induce and maintain hypocapnia were performed in 61 healthy participants, effects on temporal estimates of dynamic cerebral autoregulation (autoregulation index, ARI) were assessed to validate the most effective strategy for inducing and maintaining hypocapnia. MAIN RESULTS: The extent of initial decrease was significantly smaller in the continuous metronome strategy compared to the delayed metronome and voluntary strategies (▵ARI 0.33 ± 1.18, 2.80 ± 3.33 and 3.69 ± 2.79 respectively, p  < 0.017). SIGNIFICANCE: The use of a continuous metronome to induce hypocapnia rather than the sudden inception of an auditory stimulus appears to reduce the initial decrease in autoregulatory capacity seen in previous studies. Dysautoregulation can be minimised by continuous metronome use during hyperventilation-induced hypocapnia. This advancement in understanding of the behaviour of CA during hypocapnia permits safer delivery of CA targeted interventions, particularly in neurologically vulnerable patient populations.

Hypocapnic cerebral hypoperfusion: A biomarker of orthostatic intolerance.

The objective of the study was to identify markers of hypocapnic cerebral hypoperfusion (HYCH) in patients with orthostatic intolerance (OI) without tachycardia and without orthostatic hypotension. This single center, retrospective study included OI patients referred for autonomic evaluation with the 10 min tilt test. Heart rate, end-tidal CO2 (ET-CO2), blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery were monitored. HYCH was defined by: (1) Symptoms of OI; (2) Orthostatic hypocapnia (low ET-CO2); (3) Abnormal decline in orthostatic CBFv due to hypocapnia; 4) Absence of tachycardia, orthostatic hypotension, or other causes of low CBFv or hypocapnia. Sixteen subjects met HYCH criteria (15/1 women/men, age 38.5±8.0 years) and were matched by age and gender to postural tachycardia patients (POTS, n = 16) and healthy controls (n = 16). During the tilt, CBFv decreased more in HYCH (-22.4±7.7%, p<0.0001) and POTS (-19.0±10.3%, p<0.0001) compared to controls (-3.0±5.0%). Orthostatic ET-CO2 was lower in HYCH (26.4±4.2 (mmHg), p<0.0001) and POTS (28.6±4.3, p<0.0001) compared to controls (36.9 ± 2.1 mmHg). Orthostatic heart rate was normal in HYCH (89.0±10.9 (BPM), p<0.08) and controls (80.8 ±11.2), but was higher in POTS (123.7±11.2, p<0.0001). Blood pressure was normal and similar in all groups. It is concluded that both HYCH and POTS patients have comparable decrease in CBFv which is due to vasoconstrictive effect of hypocapnia. Blood flow velocity monitoring can provide an objective biomarker for HYCH in OI patients without tachycardia.

Carbon dioxide dynamics in relation to neurological outcome in resuscitated out-of-hospital cardiac arrest patients: an exploratory Target Temperature Management Trial substudy.

BACKGROUND: Dyscarbia is common in out-of-hospital cardiac arrest (OHCA) patients and its association to neurological outcome is undetermined. METHODS: This is an exploratory post-hoc substudy of the Target Temperature Management (TTM) trial, including resuscitated OHCA patients, investigating the association between serial measurements of arterial partial carbon dioxide pressure (PaCO2) and neurological outcome at 6 months, defined by the Cerebral Performance Category (CPC) scale, dichotomized to good outcome (CPC 1 and 2) and poor outcome (CPC 3-5). The effects of hypercapnia and hypocapnia, and the time-weighted mean PaCO2 and absolute PaCO2 difference were analyzed. Additionally, the association between mild hypercapnia (6.0-7.30 kPa) and neurological outcome, its interaction with target temperature (33 °C and 36 °C), and the association between PaCO2 and peak serum-Tau were evaluated. RESULTS: Of the 939 patients in the TTM trial, 869 were eligible for analysis. Ninety-six percent of patients were exposed to hypocapnia or hypercapnia. None of the analyses indicated a statistical significant association between PaCO2 and neurological outcome (P = 0.13-0.96). Mild hypercapnia was not associated with neurological outcome (P = 0.78) and there was no statistically significant interaction with target temperature (Pinteraction = 0.95). There was no association between PaCO2 and peak serum-Tau levels 48 or 72 h after return of spontaneous circulation (ROSC). CONCLUSIONS: Dyscarbia is common after ROSC. No statistically significant association between PaCO2 in the post-cardiac arrest phase and neurological outcome at 6 months after cardiac arrest was detected. There was no significant interaction between mild hypercapnia and temperature in relation to neurological outcome.

Incidence of Hypocapnia, Hypercapnia, and Acidosis and the Associated Risk of Adverse Events in Preterm Neonates.

BACKGROUND: Permissive hypercapnia is a lung-protection strategy. We sought to review our current clinical practice for the range of permissive hypercapnia and identify the relationship between PaCO2 and pH and adverse outcomes. METHODS: A secondary analysis of a delayed cord-clamping clinical trial was performed on all arterial blood gas tests in the first 72 h in infants < 32 weeks gestational age. All arterial blood gas values were categorized into a clinical range to determine the percent likelihood of occurring in the total sample. The univariate and multivariate relationships of severe adverse events and the time-weighted PaCO2 , fluctuation of PaCO2 , maximal and minimal PaCO2 , base excess, and pH were assessed. RESULTS: 147 infants with birthweight of 1,206 ± 395 g and gestational age of 28 ± 2 weeks were included. Of the 1,316 total samples, < 2% had hypocapnia (PaCO2 <30 mm Hg), 47% were normocapnic (PaCO2 35-45 mm Hg), 26.5% had mild hypercapnia (PaCO2 45-55 mm Hg), 13% had moderate hypercapnia (PaCO2 55-65 mm Hg), and 6.5% had severe hypercapnia (PaCO2 ≥ 65 mm Hg). There were no adverse events associated with hypocapnia. Subjects with death/severe intraventricular hemorrhage had a higher mean PaCO2 of 52.3 versus 44.7 (odds ratio [OR] 1.16, 95% CI 1.04-1.29, P = .006), higher variability of PaCO2 with a standard deviation of 12.6 versus 7.8 (OR 1.15, 95% CI 1.03-1.27, P = .01), and a lower minimum pH of 7.03 versus 7.23 (OR 0, 95% CI 0-0.06, P = .003). There was no significant difference in any variables in subjects who developed other adverse events. CONCLUSION: The routine targeting of higher than normal PaCO2 goals may lead to a low incidence of hypocapnia and associated adverse events. Hypercapnia is common, and moderate hypercapnia may increase the risk of neurologic injury and provide little pulmonary benefit.

Carbon dioxide therapy in hypocapnic respiratory failure.

Oxygen therapy, usually administered by a facemask or nasal cannulae, is the current default treatment of respiratory failure. Since respiration entails intake of oxygen and release of carbon dioxide from tissues as waste product, the notion of administering carbon dioxide in respiratory failure appears counter-intuitive. However, carbon dioxide stimulates the chemosensitive area of the medulla, known as the central respiratory chemoreceptor, which activates the respiratory groups of neurones in the brainstem and stimulates inspiration thereby initiating oxygen intake during normal breathing. This vital initiation of normal breathing is via a reduction in the pH of the cerebrospinal fluid and the medullary interstitial fluid. We hypothesise that in cases of type I respiratory failure in which the PaCO2 is low, administration of carbon dioxide by inhalation would stimulate the respiratory groups of brainstem neurones and facilitate breathing, which would be of therapeutic value. Preliminary clinical evidence in favour of this hypothesis is presented and we recommend that a formal randomised study be carried out.

Central Sleep Apnea in Patients with Congestive Heart Failure.

Central sleep apnea and Cheyne-Stokes respiration are commonly observed breathing patterns during sleep in patients with congestive heart failure. Common risk factors are male gender, older age, presence of atrial fibrillation, and daytime hypocapnia. Proposed mechanisms include augmented peripheral and central chemoreceptor sensitivity, which increase ventilator instability during both wakefulness and sleep; diminished cerebrovascular reactivity and increased circulation time, which impair the normal buffering of Paco2 and hydrogen ions and delay the detection of changes in Paco2 during sleep; and rostral fluid shifts that predispose to hypocapnia.

Arousal-Induced Hypocapnia Does Not Reduce Genioglossus Activity in Obstructive Sleep Apnea.

Study Objectives: To determine whether arousals that terminate obstructive events in obstructive sleep apnea (OSA) (1) induce hypocapnia and (2) subsequently reduce genioglossus muscle activity following the return to sleep. Methods: Thirty-one untreated patients with OSA slept instrumented with sleep staging electrodes, nasal mask and pneumotachograph, end-tidal CO2 monitoring, and intramuscular genioglossus electrodes. End-tidal CO2 was monitored, and respiratory arousals were assigned an end-arousal CO2 change value (PETCO2 on the last arousal breath minus each individual's wakefulness PETCO2). This change value, in conjunction with the normal sleep related increase in PETCO2, was used to determine whether arousals induced hypocapnia and whether the end-arousal CO2 change was associated with genioglossus muscle activity on the breaths following the return to sleep. Results: Twenty-four participants provided 1137 usable arousals. Mean ± SD end-arousal CO2 change was -0.2 ± 2.4 mm Hg (below wakefulness) indicating hypocapnia typically developed during arousal. Following the return to sleep, genioglossus muscle activity did not fall below prearousal levels and was elevated for the first two breaths. End-arousal CO2 change and genioglossus muscle activity were negatively associated such that a 1 mm Hg decrease in end-arousal CO2 was associated with an ~2% increase in peak and tonic genioglossus muscle activity on the breaths following the return to sleep. Conclusions: Arousal-induced hypocapnia did not result in reduced dilator muscle activity following return to sleep, and thus hypocapnia may not contribute to further obstructions via this mechanism. Elevated dilator muscle activity postarousal is likely driven by non-CO2-related stimuli.