Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea

Patients with obesity hypoventilation syndrome (OHS) have a lower quality of life, more healthcare expenses, a greater risk of pulmonary hypertension, and a higher mortality compared to eucapnic patients with obstructive sleep apnea (OSA). Despite significant morbidity and mortality associated with OHS, it is often unrecognized and treatment is frequently delayed. The objective of this observational study was to determine the prevalence of OHS in patients with OSA seen at the sleep disorders clinic of a large public urban hospital serving predominantly minority population and to identify clinical—not mechanistic—predictors that should prompt clinicians to measure arterial blood gases. In the first stage, we randomly selected 180 patients referred to our sleep disorders clinic between 2000 and 2004 for suspicion of OSA. From this retrospective random sample we calculated the prevalence of OHS in patients with OSA and identified independent clinical predictors using logistic regression. In the second stage, we prospectively validated these predictors in a sample of 410 consecutive patients referred to the sleep disorders clinic for suspicion of OSA between 2005 and 2006. The prevalence of OHS in patients with OSA was 30% in the retrospective random sample and 20% in the prospective sample. Three variables independently predicted OHS in both samples: serum bicarbonate level (p < 0.001), apnea–hypopnea index (p = 0.006), and lowest oxygen saturation during sleep (p < 0.001). Due to the serious morbidity associated with OHS, we selected a highly sensitive threshold of serum bicarbonate level. A threshold of 27 mEq/l had a sensitivity of 92% and a specificity of 50%. Only 3% of patients with a serum bicarbonate level <27 mEq/l had hypercapnia compared to 50% with a serum bicarbonate ≥27 mEq/l. In conclusion, OHS is common in severe OSA. A normal serum bicarbonate level excludes hypercapnia and an elevated serum bicarbonate level should prompt clinicians to measure arterial blood gases.     

Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO(2)). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (~5.8%), differences in n (2.21+/-0.03 in VC and 1.58+/-0.03 in LN; Cohen d=1.71) produced substantially weaker (~3.7x) subcortical than cortical BOLD responses relative to CMRO(2) changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot be interpreted as a quantitative reflection of underlying metabolic changes, particularly when comparing cortical and subcortical regions.     

阻塞性睡眠呼吸暂停低通气综合征发生慢性高碳酸血症相关因素探讨

目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者发生慢性高碳酸血症的相关因素。方法对苏州大学附属第二医院2004-02～2005-04收治的56例OSAHS患者进行血气分析和肺功能测定。分为高碳酸血症组和正常碳酸组、肥胖组和非肥胖组。记录患者的体重指数(BMI)、多导睡眠图(PSG)指标、肺功能测定值和血气分析值。分别比较高碳酸血症组和正常碳酸组、肥胖组和非肥胖组上述指标的差异程度。通过直线相关分析获得动脉血二氧化碳分压(PaCO2)与其他变量的相关性;有相关性的变量再通过多元线性回归分析比较各自对PaCO2变化所起的作用。结果多元回归分析显示,在高碳酸血症组,肺活量占预计值的百分比(%VC)和夜间平均脉搏血氧饱和度(SpO2)是影响日间PaCO2的两个主要变量。二者组成的模型解释了总变异的约74%(R2=0.738,P<0.001)。在肥胖组,%VC和平均SpO2也是影响PaCO2水平的两个主要变量,模型解释了总变异的79%(R2=0.792,P<0.001)。结论限制性通气功能障碍和夜间血氧饱和度降低在OSAHS患者发生慢性高碳酸血症中起主要的作用。     

Arterial carbon dioxide tension on admission as a marker of in-hospital mortality in community-acquired pneumonia

PURPOSE: Respiratory failure is the leading cause of death among patients admitted with community-acquired pneumonia. We sought to determine the association between arterial carbon dioxide tension (P(a)CO(2)) and in-hospital mortality in patients admitted with pneumonia. METHODS: We analyzed data from 2171 patients aged >or=17 years who had been admitted for community-acquired pneumonia to an acute care hospital in Edmonton, Alberta. We compared the risk of all-cause in-hospital mortality using a Cox proportional hazards model across categories of P(a)CO(2). RESULTS: Overall, in-hospital mortality was 10% (n = 218). Compared with patients with normal P(a)CO(2) values (40 to 44 mm Hg), in-hospital mortality was greater (adjusted odds ratio [OR] = 1.8; 95% confidence interval [CI]: 1.0 to 3.2) among patients with hypocapnia (P(a)CO(2) <32 mm Hg). In-hospital mortality was also greater (OR = 2.6; 95% CI: 1.5 to 4.5) in patients with hypercapnia (>or=45 mm Hg). In-hospital mortality was similar in patients with P(a)CO(2) values between 32 and 35 mm Hg (OR = 1.55; 95% CI: 0.89 to 2.79) and those with values between 36 and 39 mm Hg (OR = 1.42; 95% CI: 0.77 to 2.61). CONCLUSION: Among patients admitted with community-acquired pneumonia, in-hospital mortality was greater in those with hypocapnia or hypercapnia. These data suggest that measurement of P(a)CO(2) adds prognostic information to standard prediction rules and should be used for clinical and epidemiologic purposes to risk-stratify in-hospital patients with community-acquired pneumonia.     

允许性高碳酸血症治疗ARDS对肺力学的影响

目的探讨允许性高碳酸血症(PHC)对重度急性呼吸窘迫综合征(ARDS)肺力学及血流动力学的影响。方法观察不同潮气量(VT)时,30例重度ARDS患者肺气体交换、肺力学的改变。结果当VT从15ml/kg降至6ml/kg时,病人均出现PHC,动脉血氧分压、氧饱和度和混合静脉血氧饱和度显著降低(P<0.05)。PHC时,气道压力显著降低,气道阻力明显增高(P<0.05)。静态肺压力-容积曲线高位转折点对应的压力为(22.2±1.9)cmH2O,容积为10ml/kg。结论在实施PHC时,只有当气道平台压<20~25cmH2O时才有可能避免肺泡过度膨胀,减少呼吸机相关性肺损伤。     

Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest

Background

Arterial carbon dioxide tension (PaCO₂) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated.

Methods and results

Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO₂ and propensity score.We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO₂ (obtained within 24 h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO₂ < 35 mmHg), 6705 (40.5%) into the normo- (35–45 mmHg) and 6827 (41.3%) into the hypercapnia (>45 mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00–1.24, p = 0.04]), lower rate of discharge home (OR 0.81 [0.70–0.94, p < 0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10–1.37, p < 0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97–1.15, p = 0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03–1.32, p = 0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89–1.06, p = 0.52]). Cox-proportional hazards modelling supported these findings.

Conclusions

Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors.     

Mechanical limitation during CO2 rebreathing in young patients with cystic fibrosis

The aim of the study was to determine whether a decrease in the ventilatory response to carbon dioxide (CO2) in children with cystic fibrosis (CF) is related to a mechanical limitation of the respiratory muscle capacity. The ventilatory response during CO2 rebreathing was performed in 15 patients (mean forced expiratory volume in 1 s (FEV1): 37 +/- 21% predicted, mean arterial CO2: 41+/- 5 mmHg). The slope of the minute ventilation normalised for weight per mmHg CO2 increment correlated negatively with respiratory muscle output, assessed by the oesophageal (p = 0.002), the diaphragmatic pressure time product (p = 0.01), and the tension time index (p = 0.005). In addition, this slope was correlated with dynamic lung compliance (p < 0.0001) and FEV1 (p = 0.03) but not with airway resistance and maximal transdiaphragmatic pressure. Therefore, an excessive load imposed on the respiratory muscles explains the blunting of the ventilatory response to CO2 in young patients with CF.     

Interaction between defects in ventilatory and thermoregulatory control in mice lacking 5-HT neurons

We have previously shown that mice with near-complete absence of 5-HT neurons (Lmx1bf/f/p) display a blunted hypercapnic ventilatory response (HCVR) and impaired cold-induced thermogenesis, but have normal baseline ventilation (), core body temperature (TCore) and hypoxic ventilatory responses (HVR) at warm ambient temperatures (TAmb; 30 degrees C). These results suggest that 5-HT neurons are an important site for integration of ventilatory, metabolic and temperature control. To better define this integrative role, we now determine how a moderate cold stress (TAmb of 25 degrees C) influences ventilatory control in adult Lmx1bf/f/p mice. During whole animal plethysmographic recordings at 25 degreesC, baseline , metabolic rate , and TCore of Lmx1bf/f/p mice were reduced (P < 0.001) compared to wild type (WT) mice. Additionally, the HCVR was reduced in Lmx1bf/f/p mice during normoxic (-33.1%) and hyperoxic (-40.9%) hypercapnia. However, in Lmx1bf/f/p mice was equal to that in WT mice while breathing 10% CO2, indicating that non-5-HT neurons may play a dominant role during extreme hypercapnia. Additionally, ventilation was decreased during hypoxia in Lmx1bf/f/p mice compared to WT mice at 25 degrees C due to decreased TCore. These data suggest that a moderate cold stress in Lmx1bf/f/p mice leads to further dysfunction in ventilatory control resulting from failure to adequately maintain TCore. We conclude that 5-HT neurons contribute to the hypercapnic ventilatory response under physiologic, more than during extreme levels of CO2, and that mild cold stress further compromises ventilatory control in Lmx1bf/f/p mice as a result of defective thermogenesis.     

高碳酸血症预处理对肺缺血-再灌注损伤早期炎症反应的影响

目的观察不同程度高碳酸血症预处理对大鼠肺缺血-再灌注损伤(lung ischemia reperfusion injury,LIRI)的影响。方法雄性SD大鼠50只,2~3月龄,随机分为五组,每组10只。假手术组(S组):开胸后游离左侧肺门,不予其他处理;IR组:采用左肺原位缺血45min,再灌注180min建立大鼠左肺IR模型;L、M、H组:通过调节RR,使P_(ET)CO_2分别达到46~55mmHg(L组)、56~65mmHg(M组)、66~75mmHg(H组),预处理5 min,然后同IR组处理建立大鼠左肺IR模型。缺血-再灌注(ischemia-reperfusion,IR)180min后,采用ELISA法检测血清IL-8和IL-10浓度;处死大鼠,取肺组织标本,采用考马斯亮蓝染色法检测肺泡灌洗液(bronchial alveolar lavage fluid,BALF)中总蛋白(TP)含量,肺组织湿/干重比(W/D)、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,观察肺组织病理学变化及TNF-α蛋白阳性细胞面积。结果与S组比较,IR、L、M、H组血清IL-8浓度、肺组织病理学评分、肺组织W/D、MDA含量,以及TNF-α蛋白阳性细胞面积百分比明显升高(P0.05),SOD活性明显降低(P0.05)。与IR组比较,L、M、H组血清IL-8浓度、肺组织病理学评分、肺组织W/D、MDA含量,以及TNF-α蛋白阳性细胞面积百分比、SOD活性明显降低(P0.05)。与L组比较,H组以上各项指标均明显降低(P0.05)。IR组血清IL-10浓度明显高于S组(P0.05)。结论通过改变呼吸模式造成高碳酸血症预处理,可以抑制大鼠LIRI后氧自由基爆发和促炎细胞因子生成,降低早期炎症反应水平,减少炎性渗出,对减轻LIRI起到一定的作用,而且在P_(ET)CO_2 46~75mmHg内,随着P_(ET)CO_2升高,作用越强。