Risk Factors For Respiratory Depression Research Articles

Pediatric obstructive sleep apnea: a prospective observational study of respiratory events in the immediate recovery period after adenotonsillectomy

BackgroundAdenotonsillectomy is often curative for pediatric obstructive sleep apnea, yet children remain at high risk of respiratory complications in the postoperative period. We sought to determine the incidence and risk factors for respiratory depression and airway obstruction, as well as clinically apparent respiratory events in the post-anesthesia care unit (PACU) in high-risk children after adenotonsillectomy. MethodsIn this prospective cohort study, we enrolled 60 high-risk children having adenotonsillectomy. Our primary outcome was respiratory depression and airway obstruction in the PACU measured using a noninvasive respiratory volume monitor (RVM) and defined by episodes of predicted minute ventilation less than 40% for at least 2 min. We measured clinically apparent respiratory events using continuous observation by trained study staff. ResultsThe median (range) age of our sample was 4 years (1, 16) and 27 (45%) were female. Black and Hispanic race children comprised 80% (n = 48) of our cohort. Thirty-nine (65%) had at least one episode of PACU respiratory depression or airway obstruction measured using the RVM, while only 21 (35%) had clinically apparent respiratory events. Poisson regression demonstrated the following associations with an increase in episodes of respiratory depression and airway obstruction: BMI Z-score less than −1 (estimate 3.91; [95%CI 1.49–10.23]), BMI Z-score 1–2 (estimate 2.04; [1.20–3.48]), and two or more comorbidities (estimate 1.96; [1.11–3.46]). ConclusionsRespiratory volume monitoring in the immediate postoperative period after pediatric high-risk adenotonsillectomy identifies impaired ventilation more frequently than is clinically apparent.

Hyperlipidemia Increases Nalbuphine Brain Accumulation with Multiple Dosing without Affecting Its Analgesic Response-Its Respiratory Depression Potential Should Be Investigated in Future Studies.

Nalbuphine is associated with a significant risk of respiratory depression. Its central nervous system entry is hindered by P-glycoproteins, and lower P-glycoprotein activity is a risk factor for respiratory depression. We assessed the effect of hyperlipidemia on nalbuphine pharmacokinetics, brain and liver uptake, and analgesic response following single (2.5 mg/kg) and multiple (2.5 mg/kg/day for three days) doses in normolipidemic and hyperlipidemic rats. Trends of reduction and increase in nalbuphine Cmax and Vdss/F were observed, respectively, in hyperlipidemic rats. Negative correlations were observed between Cmax and serum lipoproteins. Serum-normalized brain and liver levels at 1 h post-dose were lower in hyperlipidemic rats, with brain and liver levels being negatively and positively correlated with TG and HDL, respectively. At steady state, marked nalbuphine accumulation was observed in hyperlipidemic rat brains (R = 1.6) compared with normolipidemic rats (R = 1.1). Nalbuphine analgesic response was not altered by hyperlipidemia at steady state. Caution should be exercised since greater brain accumulation in hyperlipidemic patients treated with nalbuphine could increase their risk of respiratory depression. Our study highlights an unexpected role of lipoproteins in drug absorption and tissue uptake. We also propose a model for reduced nalbuphine absorption based on interaction with intestinal HDL-3.

Risk Factors for Respiratory Depression Associated with Tramadol Based on the Global Pharmacovigilance Database (VigiBase).

Tramadol, a weak μ-opioid receptor agonist, has been used worldwide for pain management. It is considered to have a favorable safety profile without serious adverse events; however, safety issues of respiratory depression were proposed by regulatory governments. We aimed to examine the risk and contributing factors associated with tramadol-related respiratory depression using a real-world database, VigiBase. Disproportionality analysis of tramadol and tramadol/paracetamol was performed using proportional reporting ratios, reporting odds ratios, and information components for all drugs and opioids. Factors related to respiratory depression, including sex, age, presence of abuse, death, and various concomitant medications, were evaluated. Among 140,721 tramadol reports, respiratory depression was reported in 1126 cases, 81.3% of which were deemed serious. Five adverse events were detected as signals of tramadol-related acute central respiratory depression (ACRD) in 882 reports. A higher proportion of ACRD cases in children and adolescents was observed than all adverse events cases of tramadol. Concomitant users of CYP2D6 inhibitors, opioids, benzodiazepines, and anti-depressant drugs showed a higher proportion in ACRD cases than non-ACRD cases. ACRD was related to drug abuse and death. This pharmacovigilance study, using VigiBase, confirmed a high risk of respiratory depression (a serious, potentially fatal adverse event) secondary to the use of tramadol, especially in pediatric patients, drug abusers, or during concomitant use of opioids, benzodiazepines, or antidepressants.

Demographics, Diagnoses, Drugs, and Adjuvants in Patients on Chronic Opioid Therapy vs. Intermittent Use in a Tertiary Pediatric Chronic Pain Clinic.

Anywhere from 11.6% to 20% of pediatric and adolescent patients treated for chronic pain are prescribed opioids, but little is known about these patients. The purpose of this study was to determine the characteristics of patients on chronic opioid therapy (COT) and what therapies had been utilized prior to or in conjunction with COT. The study was a retrospective chart review of all chronic pain patients seen during 2020 with those patients on COT separated for analysis. A total of 346 unique patients were seen of which 257 were female (74.3%). The average age was 15.5 years. A total of 48 patients (13.9%) were identified as being on COT with an average age of 18.1 years. Of these, 23 (47.9%) were male which was significantly more than expected. The most common reason for patients to be receiving COT was palliative (13/48), and the second most common was sickle cell anemia (10/48). Patients on COT were significantly more likely to be male, be older, and to be concurrently prescribed benzodiazepines. Concurrent opioid and benzodiazepine therapy is a risk factor for respiratory depression and overdose. Further investigation into the increased proportion of males and benzodiazepine usage in patients on COT is warranted.

Prevalence of Gabapentinoids and Central Nervous System Depressant Drugs, and Their Association with Risk Factors for Respiratory Depression in Primary Care Patients.

Warnings have been published regarding an increased risk of severe respiratory depression in patients receiving gabapentinoids either alone or in combination with opioids and/or anxiolytics/hypnotics, especially in individuals with a respiratory risk factor. The aim is to report the prevalence of the use of gabapentinoids alone and associated with central nervous system depressant drugs, and possible associated risk factors for respiratory depression, in order to identify the most fragile population and establish intervention strategies. We performed a cross-sectional study using computerized prescription records from the northern area of Barcelona at Catalan Institute of Health for 363,007 inhabitants registered during 2021. Patients aged ≥18 years with one or more gabapentinoid prescription were included. Age, gender, polypharmacy, adjusted morbidity groups, quantity of chronic diseases, and the number of consultations per year were independent variables. Four age categories were defined (18-64 years, then 64-74, 75-84, and those aged 85 years or older). Descriptive and inferential statistics were employed. Level of statistical significance was 5% (p≤0.05). For the analysis, the SPSS program (version 22) was employed. Of the study sample, 9218 were prescribed gabapentidoids. Overall prevalence of use was 3.0% (women 3.6%, men 2.4%). On the whole, women used more drugs than men. In contrast to their younger counterparts, consumption increased 2.6 times, 3.8 times, and 4.0 times in the 65-74 age group, 75-84 age group, and those aged ≥85 years, respectively. Mean age was 65.59 (±15.80) years. Polypharmacy (5-9 drugs) was present in 41.7% of the patients and extreme polypharmacy (≥10 drugs) was present in 39.3% of the patients. Regarding renal function, 2396 patients (25.9%) had glomerular filtration that required dose adjustment (76.1% with gabapentin and 23.8% with pregabalin). In 141 patients (5.9%), a total daily dose higher than that authorized (109 with gabapentin, 29 with pregabalin) had been prescribed. The prescription of gabapentinoids combined with opioids and/or anxiolytics/hypnotics was significantly associated with (i) polypharmacy (5-9 drugs, OR: 3.42 [95% CI 3.00-3.88]; ≥10 drugs, OR 8.72 [95% CI 7.42-10.25]); (ii) quantity of chronic diseases, OR: 1.14 (95% CI 1.11-1.17); (iii) augmented number of consultations/year, OR: 1.01 (95% CI 1.00-1.01); (iv) female gender, OR: < 1 for men, OR: 0.66 (95% CI 0.60-0.73); (v) being elderly: 65-74 years, OR: 0.71 (95% CI 0.62-0.81); 75-84 years, OR: 0.62 (95% CI 0.54-0.71); ≥85 years, OR: 0.68 (95% CI 0.58-0.81); and (vi) adjusted morbidity groups, OR: 0.90 (95% CI 0.88-0.92), (p< 0.0001). Exposure to gabapentinoids occurs in a non-negligible percentage of the population. Greater numbers of combinations of gabapentinoids and opioids and/or anxiolytics/hypnotics were associated with polypharmacy, quantity of chronic diseases, and augmented number of consultations, but not with male gender, older age, and adjusted morbidity groups.

An assessment of opioids on respiratory depression in children with and without obstructive sleep apnea.

Obstructive sleep apnea is a risk factor for respiratory depression following opioid administration as well as opioid-induced hyperalgesia. Little is known on how obstructive sleep apnea status is associated with central ventilatory depression in pediatric surgical patients given a single dose of fentanyl. This was a single-center, prospective trial in children undergoing surgery requiring intubation and opioid administration. Sixty patients between the ages of 2-8years presenting for surgery at Texas Children's Hospital were recruited. Twenty non-obstructive sleep apnea controls and 30 patients with moderate to severe obstructive sleep apnea met inclusion criteria. Following induction of general anesthesia and establishment of steady-state ventilation, participants received 1mcg/kg intravenous fentanyl. Ventilatory variables (tidal volume, respiratory rate, end-tidal CO2 , and minute ventilation) were assessed each minute for 10min. The primary outcome was the extent of opioid-induced central ventilatory depression over time by obstructive sleep apnea status when compared with baseline values. Secondary aims assessed the impact of demographics and SpO2 nadir on ventilatory depression. We found no significant difference in percent decrease in respiratory rate (38.1% and 37.1%; p=.950), tidal volume (6.4% and 5.4%; p=.992), and minute ventilation (35.0L/min and 35.0L/min; p=.890) in control and obstructive sleep apnea patients, respectively. Both groups experienced similar percent increases in end-tidal CO2 (4.0% vs. 2.2%; p=.512) in control and obstructive sleep apnea patients, respectively. In pediatric surgical patients, obstructive sleep apnea status was not associated with significant differences in central respiratory depression following a single dose of fentanyl (1mcg/kg). These findings can help determine safe opioid doses in future pediatric obstructive sleep apneapatients.

Quantifying the incidence of clinically significant respiratory depression in women with and without obesity class III receiving neuraxial morphine for post-cesarean analgesia: a retrospective cohort study

BackgroundObesity is a suspected risk factor for respiratory depression following neuraxial morphine for post-cesarean analgesia, however monitoring guidelines for obese obstetric patients are based on small, limited studies. We tested the hypothesis that clinically significant respiratory depression following neuraxial morphine occurs more commonly in women with body mass index (BMI) ≥40 kg/m2 compared with BMI <40 kg/m2. MethodsWe conducted a single-center, retrospective chart review (2006–2017) of obstetric patients with clinically significant respiratory depression following neuraxial morphine, defined as: (1) opioid antagonist administration; (2) rapid response team activation (initiated in April 2010); or (3) tracheal intubation due to a respiratory event. The incidence of respiratory depression was compared between women with BMI ≥40 kg/m2 and BMI <40 kg/m2. ResultsIn total, 11 327 women received neuraxial morphine (n=1945 BMI ≥40 kg/m2; n=9382 BMI <40 kg/m2). Women with BMI ≥40 kg/m2 had higher rates of sleep apnea, hypertensive disorders, and magnesium administration. Sixteen cases of clinically significant respiratory depression occurred within seven days postpartum. The incidence did not significantly differ between groups (odds ratio 2.2, 95% CI 0.6 to 6.9, P=0.174). Neuraxial morphine was not deemed causative in any case, however women with BMI ≥40 kg/m2 had higher rates of tracheal intubation unrelated to neuraxial morphine (2/1945 vs. 0/9382, P=0.029). ConclusionsRespiratory depression in this population is rare. A larger sample (∼75 000) is required to determine whether the incidence is higher with BMI ≥40 kg/m2. Tracheal intubation was higher among the BMI ≥40 kg/m2 cohort, likely due to more comorbidities.

Low-dose prostaglandin E1 is safe and effective for critical congenital heart disease: is it time to revisit the dosing guidelines?

Prostaglandin E1 is used to maintain ductal patency in critical congenital heart disease (CHD). The standard starting dose of prostaglandin E1 is 0.05 µg/kg/minute. Lower doses are frequently used, but the efficacy and safety of a low-dose regimen of prostaglandin E1 has not been established. We investigated neonates with critical CHD who were started on prostaglandin E1 at 0.01 µg/kg/minute. We reviewed 154 consecutive patients who were separated into three anatomical groups: obstruction to systemic circulation, obstruction to pulmonary circulation, and inadequate mixing (d-transposition of the great arteries). Treatment failure rates and two commonly reported side effects, respiratory depression and seizure, were studied. A total of 26 patients (17%) required a dose increase in prostaglandin E1. Patients with pulmonary obstruction were more likely to require higher doses than patients with systemic obstruction (15/49, 31% versus 9/88, 10%, p = 0.003). Twenty-eight per cent of patients developed respiratory depression and 8% of patients needed mechanical ventilation. Prematurity (<37 week gestation) was the primary risk factor for respiratory depression. No patient required dose escalation or tracheal intubation while on transport. No patient had a seizure attributed to prostaglandin E1. Prostaglandin E1 at an initial and maintenance dose of 0.01 µg/kg/minute was sufficient to maintain ductal patency in 83% of our cohort. The incidence of respiratory depression requiring mechanical ventilation was low and was mostly seen in premature infants. Starting low-dose prostaglandin E1 at 0.01 µg/kg/minute is a safe and effective therapy for critical CHD.

Perioperative methadone prescribing and association with respiratory depression.

Over 80 percent of surgery patients experience acute post-operative pain and less than half feel their pain is adequately controlled. Patients receiving chronic opioids, including methadone, are at the highest risk of inadequate pain control. Guidelines do not provide specific recommendations for analgesia management in this population. The purpose of this study was to evaluate the association between post-operative methadone use and respiratory depression. This study was a single center, retrospective, cohort study of adult patients. Patients included were admitted to a single academic medical center from July 2016 to September 2018. Medical records of adult inpatients with an operative procedure who received perioperative methadone were reviewed. Preoperative methadone use was evaluated for all patients. Post-operative methadone dosing was compared to preoperative methadone dosing. Post-operative respiratory depression was evaluated. Logistic regression was performed to identify risk factors for respiratory depression. Two hundred ninety-eight patients were included in the study. Patients were divided into groups based on pre-operative methadone use. Over 90 percent of patients were on preoperative methadone. There were no significant differences in baseline characteristics between groups. In the initial seven post-operative days, 14.8 percent of patients had documented respiratory depression. Respiratory depression was more common among patients who were newly initiated on methadone post-operatively. Factors associated with respiratory depression included male sex, increased age, and new post-operative methadone initiation. Most patients who were administered post-operative methadone were on preoperative methadone. New post-operative methadone initiation was a risk factor for respiratory depression.

Is postoperative atelectasis following lumbar fusion more prevalent among patients with chronic opioid use?

ObjectiveChronic opioid use (COU) remains on the rise globally, acting as a marker for patient morbidity and a risk factor for adverse health outcomes. Opioid use is a risk factor for respiratory depression, which may lead to dysfunctional breathing, a known cause of atelectasis. The objective of this study was to determine whether COU is associated with increased rates of postoperative atelectasis among patients undergoing lumbar fusion. Materials & MethodsThree State Inpatient Databases were used to identify patients who underwent an elective lumbar fusion through an anterior, posterior or circumferential approach in Florida, Kentucky and New York between 2013−2015. Patients with COU and those with postoperative atelectasis were identified using ICD diagnosis codes. Three operative groups were created and subsequently matched using propensity scores in order to provide comparable cohorts for analysis. Three-to-one propensity score matching was conducted using the variables of age, sex, race, number of chronic diagnoses and geographic state of admission. Multivariable logistic regressions were used to examine the relationship between COU and postoperative atelectasis. ResultsA total of 3618 lumbar fusions were identified. Atelectasis was noted in 1.33 % of NCOU patients and 2.32 % of COU patients. On multivariable analysis, while controlling for the Elixhauser Mortality Index and patient insurance status, COU was significantly associated with atelectasis in posterior lumbar fusion (OR = 2.27; CI: 1.09–4.72; p = 0.028) and circumferential lumbar fusion (OR = 4.68; CI: 1.52–14.45; p = 0.007). The Elixhauser Mortality Index was also significantly associated with atelectasis in posterior lumbar fusion (OR = 1.08; CI: 1.04–1.11; p < 0.001) and circumferential lumbar fusion (OR = 1.09; CI: 1.03–1.16; p = 0.002). ConclusionHigher rates of postoperative atelectasis were found among patients with COU following posterior and circumferential lumbar fusions. The Elixhauser Mortality Index was also independently associated with atelectasis. Knowledge of these risks may allow for earlier identification and intervention in patients who are at risk.

Analysis of the sensitivity to hypoxemia predicted by end-tidal carbon dioxide partial pressure in painless colonoscopy and risk factors for respiratory depression

Objective To investigate the risk factors of respiratory depression and its sensitivity in predicting hypoxemia in painless colonoscopy. Methods A total of 120 patients [American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ] who underwent painless colonoscopy from February to March 2018 were enrolled. The patients were divided into a respiratory depression group (group D) and a non-respiratory depression group (group N), according to whether respiratory depression [endtidal carbon dioxide partial pressure (PETCO2) ≥50 mmHg (1 mmHg=0.133 kPa) or disappearance of waveform ≥15 s] was achieved during surgery. The following indicators of both groups were recorded: gender, age, length of examination, propofol doses, body mass index (BMI), obstructive sleep apnea syndrome (OSAS) history, the interval from respiratory depression to hypoxemia [pulse oxygen saturation (SpO2) <90%] and the interval from the onset of hypoxemia alert values to hypoxemia. Results Remarkable difference was found in age, BMI, and OSAS history between the two groups, while age and BMI were the independent risk factors for respiratory depression. According to receiver operating characteristic (ROC) curve, age, BMI, and both can predict respiratory depression to some extent. Notably, the area under the ROC curve for both age and BMI was greater, compared with age and BMI alone (P<0.05). Compared with group N, group D had advantages in predicting hypoxemia(P<0.05). Compared with traditional oxygen saturation value (SpO2), monitoring PETCO2 predicted hypoxemia earlier, with earlier respiratory depression (63.9 s) than hypoxemia on average (SpO2<90%). Conclusions Patients with older ages and high BMI in painless colonoscopy are more likely to present respiratory depression. Monitoring PETCO2 can be more sensitive to predict the occurrence of hypoxemia, providing sufficient time for our treatment of hypoxemia to guarantee patient safety. Key words: End-tidal carbon dioxide partial pressure; Risk factors; Respiratory depression; Hypoxemia

Efficacy and Safety of Deep Sedation in Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma.

Radiofrequency ablation (RFA) has been accepted as safe and effective for treating early-stage hepatocellular carcinoma (HCC). However, it often causes severe pain. Therefore, in this study, we performed RFA under deep sedation and investigated its efficacy and safety. We conducted a retrospective study including 511 HCC patients who received approximately 886 RFA treatments between December 2014 and November 2016 at our institution. Respiratory depression was defined as oxygen saturation of below 90%; and severe body movement was defined as movement caused by pain, which was managed by lowering the power of the generator. Factors associated with respiratory depression and severe body movement were examined via univariate and multivariate regression analyses. Respiratory depression occurred in 15.3% of the patients and severe body movement in 26.5% of the patients. In the multivariate analysis, BMI (≥ 25kg/m2, odds ratio [OR] = 1.75, P = 0.035) and longer ablation (≥ 10min, OR = 2.59, P = 0.002) were significant respiratory depression-related factors. Male sex (OR = 2.02, P = 0.005), Child-Pugh class A (odds ratio = 1.96, P = 0.018), and longer ablation (≥ 10min, OR = 3.03, P < 0.001) were significant factors related to severe body movement. Deep sedation for RFA can be performed safely and effectively. Higher BMI and longer ablation were risk factors for respiratory depression and male sex, Child-Pugh class A, and longer ablation were independent predictors of severe body movement during RFA under deep sedation.

Respiratory depression in the intoxicated trauma patient: are opioids to blame?

Providing effective pain management to acutely intoxicated trauma patients represents a challenge of balancing appropriate pain management with the risk of potential respiratory depression from opioid administration. The objective of this study was to quantify the incidence of respiratory depression in trauma patients acutely intoxicated with ethanol who received opioids as compared with those who did not and identify potential risk factors for respiratory depression in this population. Retrospective medical record review was conducted for subjects identified via the trauma registry who were admitted as a trauma activation and had a detectable serum ethanol level upon admission. Risk factors and characteristics compared included demographics, Injury Severity Score, Glasgow Coma Score, serum ethanol level upon arrival, urine drug screen results, incidence of respiratory depression, and opioid and other sedative medication use. A total of 233 patients were included (78.5% male). Patients who received opioids were more likely to have a higher Injury Severity Score and initial pain score on admission as compared with those who did not receive opioids. Blood ethanol content was higher in patients who did not receive opioids (0.205 vs 0.237 mg/dL, P = .015). Patients who did not receive opioids were more likely to be intubated within 4 hours of admission (1.7% vs 12.1%, P = .02). Opioid administration was not associated with increased risk of respiratory depression (19.7% vs 22.4%, P = .606). Increased cumulative fentanyl dose was associated with increased risk of respiratory depression. Increased cumulative fentanyl dose, but not opioid administration alone, was found to be a risk factor for respiratory depression.

Postoperative opioid-induced respiratory depression: a closed claims analysis.

Postoperative opioid-induced respiratory depression (RD) is a significant cause of death and brain damage in the perioperative period. The authors examined anesthesia closed malpractice claims associated with RD to determine whether patterns of injuries could guide preventative strategies. From the Anesthesia Closed Claims Project database of 9,799 claims, three authors reviewed 357 acute pain claims that occurred between 1990 and 2009 for the likelihood of RD using literature-based criteria. Previously cited patient risk factors for RD, clinical management, nursing assessments, and timing of events were abstracted from claim narratives to identify recurrent patterns. RD was judged as possible, probable, or definite in 92 claims (κ = 0.690) of which 77% resulted in severe brain damage or death. The vast majority of RD events (88%) occurred within 24 h of surgery, and 97% were judged as preventable with better monitoring and response. Contributing and potentially actionable factors included multiple prescribers (33%), concurrent administration of nonopioid sedating medications (34%), and inadequate nursing assessments or response (31%). The time between the last nursing check and the discovery of a patient with RD was within 2 h in 42% and within 15 min in 16% of claims. Somnolence was noted in 62% of patients before the event. This claims review supports a growing consensus that opioid-related adverse events are multifactorial and potentially preventable with improvements in assessment of sedation level, monitoring of oxygenation and ventilation, and early response and intervention, particularly within the first 24 h postoperatively.

Opioids prescription for symptoms relief and the impact on respiratory function: updated evidence.

Opioids are used for treating dyspnea and other symptoms in oncological and nononcological patients. The relief of respiratory fatigue and anxiety that these opioids offer is well known. One of the scarcely frequent, but very much feared, side-effects is respiratory depression. The purpose of this review is to determine whether or not the situation of an advanced-stage patient under palliative care and the use of opioids are risk factors for respiratory depression. Studies conducted on respiratory function and opioids have proliferated in the past 10 years, but there is no recent review that groups the results together and evaluates their safe use in end-stage patients. A bibliographic review found three randomized double-blinded placebo-controlled studies and five prospective studies, six of which showed that opioids significantly relieve dyspnea (P<0.001). The use of morphine for symptomatic relief does not significantly change the level of saturation of oxygen in the blood. In addition, the functional studies do not indicate that the use of opioids for dyspnea relief causes high CO2 levels in blood (P=0.05). The opioids used for treating dyspnea do not significantly compromise respiratory function; they are safe and effective.

Tramadol can selectively manage moderate pain in children following European advice limiting codeine use.

The European Medicine Agency recommendations limiting codeine use in children have created a void in managing moderate pain. We review the evidence on the pharmacokinetic, pharmacodynamic and safety profile of tramadol, a possible substitute for codeine. Tramadol appears to be safe in both paediatric inpatients and outpatients. It may be appropriate to limit the current use of tramadol to monitored settings in children with risk factors for respiratory depression, subject to further safety evidence.

The Treatment of Central Sleep Apnea Syndromes in Adults: Practice Parameters with an Evidence-Based Literature Review and Meta-Analyses

The International Classification of Sleep Disorders, Second Edition (ICSD-2) distinguishes 5 subtypes of central sleep apnea syndromes (CSAS) in adults. Review of the literature suggests that there are two basic mechanisms that trigger central respiratory events: (1) post-hyperventilation central apnea, which may be triggered by a variety of clinical conditions, and (2) central apnea secondary to hypoventilation, which has been described with opioid use. The preponderance of evidence on the treatment of CSAS supports the use of continuous positive airway pressure (CPAP). Much of the evidence comes from investigations on CSAS related to congestive heart failure (CHF), but other subtypes of CSAS appear to respond to CPAP as well. Limited evidence is available to support alternative therapies in CSAS subtypes. The recommendations for treatment of CSAS are summarized as follows: CPAP therapy targeted to normalize the apnea-hypopnea index (AHI) is indicated for the initial treatment of CSAS related to CHF. (STANDARD)Nocturnal oxygen therapy is indicated for the treatment of CSAS related to CHF. (STANDARD)Adaptive Servo-Ventilation (ASV) targeted to normalize the apnea-hypopnea index (AHI) is indicated for the treatment of CSAS related to CHF. (STANDARD)BPAP therapy in a spontaneous timed (ST) mode targeted to normalize the apnea-hypopnea index (AHI) may be considered for the treatment of CSAS related to CHF only if there is no response to adequate trials of CPAP, ASV, and oxygen therapies. (OPTION)The following therapies have limited supporting evidence but may be considered for the treatment of CSAS related to CHF after optimization of standard medical therapy, if PAP therapy is not tolerated, and if accompanied by close clinical follow-up: acetazolamide and theophylline. (OPTION)Positive airway pressure therapy may be considered for the treatment of primary CSAS. (OPTION)Acetazolamide has limited supporting evidence but may be considered for the treatment of primary CSAS. (OPTION)The use of zolpidem and triazolam may be considered for the treatment of primary CSAS only if the patient does not have underlying risk factors for respiratory depression. (OPTION)The following possible treatment options for CSAS related to end-stage renal disease may be considered: CPAP, supplemental oxygen, bicarbonate buffer use during dialysis, and nocturnal dialysis. (OPTION) .

Intravenous Valproate Use in Bipolar II Disorder After Gastric Bypass Surgery

Intravenous Valproate Use in Bipolar II Disorder After Gastric Bypass Surgery

Respiratory depression in adult patients with intravenous patient-controlled analgesia.

Patient-controlled analgesia (PCA) has been widely implemented to provide better pain relief and increased patient satisfaction with relatively few side effects. However, patients using intravenous (i.v.) PCA are at increased risk for specific adverse effects, especially respiratory depression. A review of the literature from 1990 to present was done to identify the incidence and risk factors for respiratory depression and recommendations for care. Several studies have documented the incidence of respiratory depression with i.v. PCA; rates ranged from 0.19% to 5.2%. Variation in incidence existed because authors defined respiratory depression differently. Methods for monitoring oxygenation include sedation; respiratory rate, depth, and rhythm, and oxygen saturation using pulse oximetry. No single parameter is the single indicator for respiratory depression. Risk factors for respiratory depression with i.v. PCA include age greater than 70 years; basal infusion with i.v. PCA; renal, hepatic, pulmonary, or cardiac impairment; sleep apnea (suspected or history); concurrent central nervous system depressants; obesity; upper abdominal or thoracic surgery; and i.v. PCA bolus > 1 mg. Structures and processes should be in place to guide appropriate dosing, identify risk factors, and activate pertinent monitoring and frequency. Finally, respiratory depression occurs infrequently in comparison to the 10% of patients who are undertreated for pain.