Evidence Of Hypoventilation Research Articles

Sleep-disordered breathing in school-aged children with Prader-Willi syndrome.

Studies of sleep-disordered breathing (SDB) in children with Prader-Willi syndrome (PWS) have focused on early childhood and growth hormone (GH)-naïve children, but little is known about older children, including those on long-term GH therapy. This study aimed to describe the nature and prevalence of SDB in school-aged children with PWS in the growth hormone era. This retrospective single-center chart review included children aged 6-18 years with PWS who had overnight polysomnography not involving respiratory support over 5 years (2012-2017). The main outcome measures were the presence of obstructive sleep apnea, central sleep apnea, or hypoventilation defined by an elevated transcutaneous partial pressure of carbon dioxide (TcPCO2) as per standard pediatric criteria. Seventeen children (8 males; median age 11.6 years, range 6.6-16.1 years) were included. Fifteen demonstrated SDB of different types: central sleep apnea (18%), obstructive sleep apnea (24%), both obstructive and central sleep apnea (29%), or hypoventilation without obstructive or central sleep apnea (18%). Twelve (71%) children had evidence of hypoventilation. Those with hypoventilation had a higher central apnea-hypopnea index but no difference in the obstructive apnea-hypopnea index, age, sex, growth parameters, or the presence of scoliosis or sleep-related symptoms compared with those without hypoventilation. Sleep-related hypoventilation is common in school-aged children with PWS. The presence of central sleep apnea, including the quantification of central hypopneas, but not obstructive sleep apnea or clinical factors, predicted the presence of hypoventilation. Long-term polysomnography surveillance in children with PWS should include identification of central hypopneas and measurement of continuous pCO2. Schaefer J, Davey MJ, Nixon GM. Sleep-disordered breathing in school-aged children with Prader-Willi syndrome. J Clin Sleep Med. 2022;18(4):1055-1061.

0675 Nocturnal Oxygen Supplementation With Positive Airway Pressure Therapy For Obesity Hypoventilation Syndrome: Clinical Predictors And Liberation From Oxygen

Abstract Introduction Obesity hypoventilation syndrome (OHS) is associated with a high morbidity and mortality. Many patients require nocturnal supplemental oxygen on top of positive airway pressure (PAP) therapy for hypoxemia independent of apneic events. We need to clinically identify patients likely to require nocturnal oxygen supplementation. Follow up is essential as with adequate control of sleep apnea, hypoxia improves and liberation from nocturnal oxygen supplementation may be achievable. Methods Researchers obtained a list of patients with coding diagnosis of OHS, seen at the Jefferson Sleep Center between November 2016 and September 2019. Patients with BMI of ≥ 30 and evidence of hypoventilation were included. Hypoventilation was defined as an elevated CO2 level of ≥ 45 mmHg on blood gas analysis, elevated serum bicarbonate level of ≥ 27 mmol/L or by evidence of nocturnal hypoventilation by AASM criteria on polysomnography. Patients with pulmonary and neuromuscular disorders were excluded Results Out of 189 patients reviewed, 36 met the inclusion and exclusion criteria. Nineteen patients (53%) required nocturnal oxygen supplementation. A higher serum bicarbonate level of 33 mmol/L against 30 mmol/L (p=0.0078) and a lower resting awake SaO2 of 89% versus 95% (p <0.01) were observed in the oxygen supplementation group. In polysomnographic data, the oxygen supplementation group had lower SaO2 nadir of 67% versus 73% (p=0.026) and had a longer time with SaO2 <88% at 238.2 minutes versus 65.5 minutes (p <0.01). Nine out of the 19 patients (47%) underwent nocturnal oximetry on PAP and room air. Of these, 4 patients (44%) were liberated from oxygen. Conclusion Fifty three percent of patients with OHS required nocturnal oxygen supplementation on top of PAP therapy. Higher serum bicarbonate level and lower resting awake SaO2 are potential clinical predictors of nocturnal oxygen supplementation. After nocturnal oximetry on PAP, 44% were successfully liberated from supplemental oxygen. Support

Less Is More: Sleep Disordered Breathing and Medication

SESSION TITLE: Student/Resident Case Report Poster - Sleep Disorders SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Opioids and benzodiazepines can worsen or precipitate sleep disordered breathing (central and obstructive), sleep-related hypoxemia/hypoventilation and result in periodic or erratic breathing patterns. CASE PRESENTATION: A 62 year old woman with a history of chronic headache/back pain, anxiety, lacunar infarction, cerebral amyloid angiopathy, hypertension, Hashimoto’s thyroiditis and diabetes mellitus was referred to the sleep clinic. She was diagnosed with OSA of unknown severity over 10 years ago. She underwent 3 follow up polysomnograms (PSG) and was on bi-level PAP in the spontaneous mode at 25/20 cm water pressure with supplemental oxygen bled in at 4 L/min at the time of presentation. In the same time interval, dependence on opioid/benzodiazepine medication had escalated. She complained of severe daytime sleepiness, falling asleep in conversation and at meals with an Epworth Sleepiness Score of 17. She had ongoing issues with imbalance,falls, cognitive impairment and chronic pain. BMI was 33. PSG revealed an AHI of 25, RDI of 37 and central apnea (CA) index of 4/hour. On CPAP, AHI was 32 and CA index 28. On Bi-Level PAP in the spontaneous mode, AHI was 81, mostly CA. On adaptive servoventilation (ASV) at maximal EPAP, AHI was 28 with persistent CA. She was prescribed CPAP at 10 cm water as most obstructive events appeared to be eliminated at this pressure, with the understanding that it was crucial to her therapy and symptoms to decrease the use of opioid/benzodiazepine medications. Over the next 2 months, she successfully decreased diazepam from 20 to 5mg daily, oxycodone ER from 240 to 80mg and short-acting oxycodone from qid to a once daily dose. Subsequent PSG showed elimination of most sleep disordered breathing/hypoxemia on CPAP at 12 cm water and no evidence of hypoventilation on arterial blood gas. DISCUSSION: Prior research has shown a dose-response relationship between opioid/benzodiazepine medications and sleep disordered breathing but this varies depending on the type of drug. It can be challenging to control sleep disordered breathing in these patients. Although difficult, we have to encourage patients to decrease/discontinue these medications safely in tandem with optimizing PAP therapy. CONCLUSIONS: CPAP therapy alone was sufficient in our complex patient after significantly decreasing opioid and benzodiazepine medications. Reference #1: Webster LR, Choi Y, Desai H, Webster L, Grant BJ. Sleep-disordered breathing and chronic opioid therapy. Pain Med. 2008 May-Jun;9(4):425-32 Reference #2: Correa D, Farney RJ, Chung F, Prasad A, Lam D, Wong J. Chronic opioid use and central sleep apnea: a review of the prevalence, mechanisms, and perioperative considerations. Anesth Analg. 2015 Jun;120(6):1273-85. Reference #3: Mason M, Cates CJ, Smith I. Effects of opioid, hypnotic and sedating medications on sleep-disordered breathing in adults with obstructive sleep apnoea. Cochrane Database Syst Rev. 2015 Jul 14;7:CD011090. DISCLOSURE: The following authors have nothing to disclose: Brendon Colaco, Meghna Mansukhani No Product/Research Disclosure Information

Obesity-related pulmonary arterial hypertension in rats correlates with increased circulating inflammatory cytokines and lipids and with oxidant damage in the arterial wall but not with hypoxia.

Obesity is causally linked to a number of comorbidities, including cardiovascular disease, diabetes, renal dysfunction, and cancer. Obesity has also been linked to pulmonary disorders, including pulmonary arterial hypertension (PAH). It was long believed that obesity-related PAH was the result of hypoventilation and hypoxia due to the increased mechanical load of excess body fat. However, in recent years it has been proposed that the metabolic and inflammatory disturbances of obesity may also play a role in the development of PAH. To determine whether PAH develops in obese rats in the absence of hypoxia, we assessed pulmonary hemodynamics and pulmonary artery (PA) structure in the diet-resistant/diet-induced obesity (DR/DIO) and Zucker lean/fatty rat models. We found that high-fat feeding (DR/DIO) or overfeeding (Zucker) elicited PA remodeling, neomuscularization of distal arterioles, and elevated PA pressure, accompanied by right ventricular (RV) hypertrophy. PA thickening and distal neomuscularization were also observed in DIO rats on a low-fat diet. No evidence of hypoventilation or chronic hypoxia was detected in either model, nor was there a correlation between blood glucose or insulin levels and PAH. However, circulating inflammatory cytokine levels were increased with high-fat feeding or calorie overload, and hyperlipidemia and oxidant damage in the PA wall correlated with PAH in the DR/DIO model. We conclude that hyperlipidemia and peripheral inflammation correlate with the development of PAH in obese subjects. Obesity-related inflammation may predispose to PAH even in the absence of hypoxia.

Postoperative Hypoxemia: Common, Undetected, and Unsuspected After Bariatric Surgery

Patients undergoing gastric bypass are at greater than ordinary risk for postoperative respiratory insufficiency, presumably related to obstructive sleep apnea (OSA) and patient-controlled analgesia (PCA). This study was proposed to quantify the magnitude of the problem. Fifteen patients undergoing gastric bypass had oxygen saturation (SpO(2)) recorded continuously, but not displayed, for 24h postoperatively; eight also had arterial blood analysis every 4h. All received narcotic PCA. SpO(2)<90% lasting more than 10 s was reviewed. Results are mean+/-SEM. Mean age was 44+/-4 y, and mean BMI was 48+/-2kg/m(2); 77% had OSA. Every patient had more than one episode with SpO(2)<90% for longer than 30s undetected by routine monitoring; most had multiple episodes. Nadir SpO(2) averaged 75% +/- 8%. Mean longest duration of desaturation below 90% averaged 21+/-15min. Mean PaCO(2) was 37+/-3mm Hg; maximum PaCO(2) was 47mm Hg. Severe and prolonged episodes of hypoxemia were a consistent finding, despite aggressive preoperative diagnosis and treatment of OSA, including use of CPAP postoperatively. Although some postoperative hypoventilation was expected, the degree and frequency of desaturation were surprising. No patient exhibited arterial PaCO(2) evidence of hypoventilation. No patient experienced cardiopulmonary arrest/instability, in spite of severe, repeated episodes of hypoxemia. In no instance was a significant hypoxemic episode suspected or detected. Continuous pulse oximetry monitoring, with an audible alarm set for a saturation less than 90% for 10 s, would have alerted providers to 100% of significant hypoxemic episodes. Our recommendation is routinely monitoring (with alarm capability enabled) every bariatric surgical patient, to prevent such occurrence.

Respiratory function during parenteral opioid titration for cancer pain

Background: Respiratory depression is the most feared opioid-related side-effect yet research on the topic is sparse. We evaluated changes in respiratory parameters during parenteral opioid titration for cancer pain to determine if opioid titration was associated with evidence of hypoventilation. The primary outcome measure was to measure changes in end-tidal CO2 (ET-CO2) during opioid titration to pain control. Methods: Subjects with severe cancer pain admitted for parenteral opioid titration for poorly controlled pain were eligible. Those who were oxygen dependent were excluded. ET-CO2, O2 saturation, respiratory rate (RR), and vital signs were monitored daily until pain control was achieved. Results: 30 patients completed the study of which 29 are reported. The mean ET-CO2 at initial evaluation was 33.39 ∓ 5.0 and 34.79 ∓ 5.7 mmHg at pain control (P =0.14, 95% CI -0.5 to 3.3). None had an ET-CO2 ≥50 mmHg. All maintained O2 saturation ≥92%. RR dropped transiently below 10/minute in two subjects. Conclusions: Parenteral opioid titration for relief of cancer pain was not associated with respiratory depression as demonstrated by significant changes in ET-CO2 or oxygen saturation in non-oxygen dependent cancer patients.

Changes in oxygen saturation and transcutaneous carbon dioxide and oxygen levels in patients undergoing fibreoptic bronchoscopy

Patients undergoing bronchoscopy are usually monitored with pulse oximetry to measure arterial oxygen saturation, but this can fail to detect hypoventilation, particularly if added inspired oxygen is used. Transcutaneous oxygen and carbon dioxide tensions can be measured; the later reflecting respiratory drive. We compared transcutaneous PO2 and PCO2 values with oxygen saturation in patients undergoing day-case bronchoscopy, to see if this information would further improve the safety of the bronchoscopic procedure. Twenty-two consecutive patients undergoing routine fibreoptic bronchoscopy (15 male, mean age 62.3 years; range 45-82 years), were studied using pulse oximetry (OXImeter, Radiometer) and transcutaneous PCO2/PO2 monitoring (TCM3, TINA, Radiometer). We documented a statistically significant increase in transcutaneous PCO2 from mean (SD) stable baseline levels of 5.8 (0.3) kPa (range 4.2-7.9 kPa) to mean peak levels during bronchoscopy of 7.0 (1.0) kPa (range 5.0-8.7 kPa). The time to first adverse change in transcutaneous PCO2 (P = 0.046) and PO2 (P = 0.035) occurred more rapidly than reduction in oxygen saturation in 19 of the 22 cases; median times for change in PCO2 of 67 s (range 10-1800 s), PO2 of 120 s (range 26-559 s) and oxygen saturation of 174 s (range 43-1332 s), timed from administration of i.v. sedation prior to each bronchoscopy. Transcutaneous PCO2/PO2 monitoring during fibreoptic bronchoscopy provided evidence of hypoventilation with significantly elevated levels of transcutaneous PCO2. This method of monitoring provides an earlier indication of respiratory depression during fibreoptic bronchoscopy compared with pulse oximetry.

Acid-Base Abnormalities Associated with Cocaine Toxicity in Emergency Department Patients

There is little information on the prevalence and clinical presentation of acid-base abnormalities associated with cocaine toxicity. To address these issues, arterial blood gas results were evaluated in 156 cocaine-associated emergency department patient visits. Arterial blood gas results were obtained as part of the patient's clinical assessment. The majority of patients (52%) had a normal pH (7.35 to 7.45). Thirty-three percent of patients were acidotic, with a pH between 6.4 and 7.35. In 33 patients the acidosis was metabolic, with a HCO3- of 14 +/- 6 mmol/L. The acidosis was primarily respiratory in 18 patients, with evidence of hypoventilation. Hypoventilation was generally secondary to chest trauma or decreased mental status. Alkalosis (pH > 7.45) was observed in 15% of patients, and was usually respiratory, as evidenced by tachypnea and a low PCO2. These results indicate that metabolic and respiratory acid-base abnormalities are common during cocaine toxicity. Acidosis and alkalosis were associated with numerous patient presentations, including chest pain, shortness of breath, decreased mental status, trauma, and seizures. Acid-base abnormalities do not appear to be associated with a specific route of cocaine self-administration. Patients with a history of potential cocaine toxicity should be evaluated for acid-base abnormalities.

Acid-base abnormalities associated with cocaine toxicity in emergency department patients.

There is little information on the prevalence and clinical presentation of acid-base abnormalities associated with cocaine toxicity. To address these issues, arterial blood gas results were evaluated in 156 cocaine-associated emergency department patient visits. Arterial blood gas results were obtained as part of the patient's clinical assessment. The majority of patients (52%) had a normal pH (7.35 to 7.45). Thirty-three percent of patients were acidotic, with a pH between 6.4 and 7.35. In 33 patients the acidosis was metabolic, with a HCO3- of 14 +/- 6 mmol/L. The acidosis was primarily respiratory in 18 patients, with evidence of hypoventilation. Hypoventilation was generally secondary to chest trauma or decreased mental status. Alkalosis (pH > 7.45) was observed in 15% of patients, and was usually respiratory, as evidenced by tachypnea and a low PCO2. These results indicate that metabolic and respiratory acid-base abnormalities are common during cocaine toxicity. Acidosis and alkalosis were associated with numerous patient presentations, including chest pain, shortness of breath, decreased mental status, trauma, and seizures. Acid-base abnormalities do not appear to be associated with a specific route of cocaine self-administration. Patients with a history of potential cocaine toxicity should be evaluated for acid-base abnormalities.

32 EVALUATION OF TOLOZOLINE TEST IN THE TREATMENT OF PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN (PPHN) BY DOPPLER ECHOCARDIOGRAPHY

To reverse pulmonary hypertension and to improve hypoxemia in PPHN, tolazoline (TZ) was tested to assess its ability to decrease pulmonary resistances. We aim to study the response to TZ vasodilation by Doppler echocardiography. We sequentially studied profiles of blood velocities in the left pulmonary artery. Through the second intercostal space, the zero angle incidence beam with the LPA allows reproducibility of repeated measurements. The ductal flow was recorded arid gradient calculated. After baseline, TZ bolus infusion was started at 1 mg/kg for 15 min, then increased by steps of 1 mg/kg if no response. Measurements were done every 5 min during the test. Material: The cohort included seven cases of PPHN:Diaphragmatic hernia, respiratory distress syndrome, Strepto, Coli and Mycoplasma sepsis. Results: the different responses were I-Immediate increased pulmonary blood flow and increase in PaO2, 2-TZ dose dependent increased PBF, 3-immediaic increase in flow and deferred increase in PaO2, 4 -Absence of response. In conclusion, Doppler evaluation of PBF, during TZ infusion, demonstrates immediate response on PBF allowing dose adaptation. It also demonstrates the magnitude of reversed shunt across the ductus to increase diastolic PBF. Transductal gradient gives estimation of pulmonary arterial pressure. It shows presence of intrapulmonary right to left shunt and evidence of hypoventilation. Then increased doses of TZ leading to ominous side-effects are avoided.

Ventilation in conscious dogs during acute and chronic hypercapnia.

Minute ventilation was measured in conscious dogs, at rest and during exercise (1 mph), over 60 min immediately following the acute inhalation of 5% carbon dioxide in air and at 2, 4, 7, and 14 days while breathing the same gas mixture in a chamber. The dogs were also studied in the immediate period of air recovery from chronic hypercapnia and 1 day later. Control studies were carried out with the dogs breathing air in the chamber under comparable conditions. A triphasic ventilation change was ovserved in dogs at rest over the 14 days of hypercapnia. After an initial marked increase in ventilation during acute hypercapnia, ventilation returned to control levels by 2 days and then appeared to be elevated above control studies from 4 to 14 days at a time when blood acid-base balance became compensated. When the same dogs were studied during exercise, ventilation was also not different from air control at 2 days of hypercapnia; however during exercise, unlike the resting studies, there was only a tendency for a secondary increase in ventilation at 7 and 14 days of hypercapnia. During the immediate recovery from chronic hypercapnia when the dogs breathed air there was no evidence of hypoventilation either at rest or exercise despite arterial alkalosis. At 24 h of recovery it appeared that dogs while at rest had a slightly reduced ventilatory response to 5% carbon dioxide relative to control studies. The findings provide suggestive evidence that other factors, in addition to acid-base balance, might contribute to the regulation of ventilation during chronic hypercapnia and the recovery from chronic hypercapnia.