Effects of opioids on ventilation and hemodynamics

Opioids are most commonly used for treatment of severe pain. However, the fear of respiratory depression has restricted the use of opioids. Depending on the monitoring system used, different modes of opioid respiratory effects have been noted in previous studies. All opioids also cause alterations in hemodynamics at least to some extent. The main goal of this series of investigations was to elucidate the native ventilatory and hemodynamic effects of different opioids. Studies I-IV each involved 8 healthy male volunteers. Study V involved 13 patients with lower or upper extremity traumas. The opioids studied were morphine, oxycodone, pethidine, fentanyl, alfentanil, tramadol and ketamine. The respiratory parameters used in this study were breathing pattern measured with respiratory inductive plethysmography, gas exchange measured with indirect calorimetry, blood gas analysis and pulse oximetry. Hemodynamics was measured with arterial blood pressure, heart rate and oxygen consumption. Plasma catecholamine and histamine concentrations were also determined. All opioids studied caused an alteration in respiratory function. Respiratory rate, alveolar ventilation and minute ventilation decreased, while tidal volume increased in most situations. Breathing pattern was also significantly affected after opioid administration. The respiratory depression caused by oxycodone was deeper than the one caused by same dose of morphine. An equianalgesic dose of tramadol caused markedly smaller respiratory depression compared to pethidine. The potency ratio for respiratory depression of fentanyl and alfentanil is similar to analgesic potency ratio studied elsewhere. Racemic ketamine attenuated the respiratory depression caused by fentanyl, if measured with minute ventilation. However, this effect was counteracted by increased oxygen consumption. Supplemental oxygen did not offer any benefits, nor did it cause any atelectasis when given to opioid treated trauma patients. Morphine caused a transient hemodynamic stimulation, which was accompanied by an increase in oxygen consumption. Oxycodone, alfentanil, fentanyl, tramadol and pethidine infusions had minimal effects on hemodynamics. Plasma catecholamine concentrations were increased after high dose opioid administration. Plasma histamine concentrations were not elevated after morphine nor oxycodone administration. Respiratory depression is a side effect noted with all opioids. The profile of this phenomenon is quite similar with different opioid-receptor agonists. The hemodynamic effects of opioids may vary depending on the opioid used, morphine causing a slight hemodynamic stimulation. However, all opioids studied could be considered hemodynamically stable.Opiodit (morfiinin kaltaiset lääkeaineet) ovat laajassa käytössä vaikean kivun hoidossa. Opioidien asianmukaista käyttöä on kuitenkin rajoittanut pelko niiden aiheuttamasta hengityslamasta. Näitä hengitysvaikutuksia on aiemmin tutkittu varsin runsaasti ja tulokset näistä tutkimuksista ovat osin ristiriitaisia. Hengitysvaikutusten lisäksi opiodeilla on vaikutuksia myös verenkiertoon. Tässä tutkimuksessa selvitettiin eri opioidien itsenäisiä vaikutuksia hengitykseen ja verenkiertoon. Tutkimukset tehtiin terveillä vapaaehtoisilla sekä akuutisti raajoihin vammautuneilla potilailla. Tutkimuksissa käytetyt opioidit olivat morfiini, oksikoni, petidiini, fentanyyli, alfentaniili, tramadoli sekä lisäksi ei-opioidi ketamiini. Hengityksen arviointiin käytettiin respiratorista induktiivista pletysmografiaa, jolla mitattiin hengitysmallin muutoksia; epäsuoraa kalorimetriaa, jolla mitattiin kaasujen vaihtoa; pulssioksimetriaa sekä verikaasuanalyysiä. Verenkierron arvioinnissa käytettiin suoraa verenpaineen mittausta sekä syketaajuuden että hapenkulutuksen mittaamista. Lisäksi mitattiin plasman katekoliamiinipitoisuuksia ja histamiinipitoisuuksia. Kaikki tutkitut opioidit aiheuttivat muutoksia hengitykseen. Hengitystaajuus, alveoliventilaatio ja minuuttiventilaatio laskivat, sen sijaan kertahengitystilavuus kohosi opioidien annon jälkeen. Oksikoni aiheutti syvemmän hengityslaman kuin sama annos morfiinia. Tramadolin vaikutus hengitykseen oli selvästi vähäisempi kuin vastaavan annoksen petidiiniä. Fentanyylin ja alfentaniilin hengitystä lamaava annossuhde oli sama kuin niiden kipua lievittävien annosten suhde. Ketamiini vähensi fentanyylin aiheuttamaa minuuttiventilaation laskua, mutta samanaikaisesti havaittiin hapenkulutuksen lisääntyminen, joka johti matalaan valtimoveren happiarvoon. Traumapotilaille kipulääkityksen yhteydessä annosteltu lisähappi ei tarjonnut mitään etuja potilaiden hengityksen turvaamiseksi, mutta toisaalta sen antoon ei havaittu liittyvän haittavaikutuksiakaan. Morfiinin annostelu aiheutti lyhytaikaisen verenkierron ja hapenkulutuksen kiihtymisen. Oksikonin, fentanyylin, alfentaniilin, tramadolin ja petidiinin todettiin aiheuttavan varsin vähäisiä muutoksia verenkiertoon. Plasman katekoliamiinipitoisuudet olivat koholla suurien opioidiannosten jälkeen. Plasman histamiinipitoisuudet eivät nousseet morfiinin eikä oksikonin annon yhteydessä. Kaikki opioidit aiheuttivat ainakin jossain määrin hengityslamaa. Tosin varsin suuriakin opiodiannoksia voidaan turvallisesti antaa potilaille, joilla on kipua eivätkä saa muita hengitystä lamaavia lääkeaineita. Tutkitut opioidit ylläpitivät vakaata verenkiertoa, ainoastaan morfiinin annosteluun havaittiin liittyvän ohimenevä verenkierron ja hapenkulutuksen lisääntyminen

Neurodevelopmental and neuroradiologic outcomes in patients with univentricular heart aged 5 to 7 years: Related risk factor analysis

ObjectiveDespite improved survival and neurodevelopmental outcome, children with hypoplastic left heart syndrome and other forms of univentricular heart remain at increased risk for cognitive, motor, and other neurologic deficits.MethodsWe examined 27 children with hypoplastic left heart syndrome or other forms of univentricular heart at a median age of 5.70 years (range 4.99–7.51 years) and performed brain computed tomography or magnetic resonance imaging on 20. Possible risk factors were correlated with outcome.ResultsMean full-scale IQ among patients with hypoplastic left heart syndrome was 86.7; that among patients with other forms of univentricular heart was 89.1, with both differing significantly from the expected population mean (P = .015 and P = .029, respectively). Cerebral palsy was diagnosed in 1 of 7 patients with hypoplastic left heart syndrome and 2 of 20 with other forms of univentricular heart. Brain computed tomography or magnetic resonance imaging revealed ischemic changes and infarcts or atrophy in 5 of 8 patients who had undergone the Norwood procedure and in 2 of 12 of those who had not (P = .062). Abnormal computed tomographic findings correlated significantly with lower full-scale IQ (P = .045) and verbal IQ (P = .02). In the multiple linear regression model, diuresis the third day after the primary operation and cardiopulmonary bypass time in the bidirectional Glenn operation correlated significantly with the primary outcome of full-scale IQ.ConclusionIn children with univentricular heart, intellectual and neurologic deficits are common. Perioperative and postoperative risk factors related to the primary phase and bidirectional Glenn operation contribute to these deficits

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.Peer reviewe

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk

Acute Kidney Injury After Cardiac Surgery by Complete KDIGO Criteria Predicts Increased Mortality

Objectives: Acute kidney injury (AKI) occurs frequently after cardiac surgery and is associated with increased mortality. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria for diagnosing AKI include creatinine and urine output values. However, the value of the latter is debated. The authors aimed to evaluate the incidence of AKI after cardiac surgery and the independent association of KDIGO criteria, especially the urine output criterion, and 2.5-year mortality. Design: Prospective, observational, cohort study. Setting: Single-center study in a university hospital. Participants: The study comprised 638 cardiac surgical patients from September 1, 2011, to June 20, 2012. Interventions: None. Measurements and Main Results: Hourly urine output, daily plasma creatinine, risk factors for AKI, and variables for EuroSCORE II were recorded. AKI occurred in 183 (28.7%) patients. Patients with AKI diagnosed using only urine output had higher 2.5-year mortality than did patients without AKI (9/53 [17.0%] v 23/455 [5.1%], p = 0.001). AKI was associated with mortality (hazard ratios [95% confidence intervals]: 3.3 [1.8-6.1] for KDIGO I; 5.8 [2.7-12.1] for KDIGO 2; and 7.9 [3.5-17.6]) for KDIGO 3. KDIGO stages and AKI diagnosed using urine output were associated with mortality even after adjusting for mortality risk assessed using EuroSCORE II and risk factors for AKI. Conclusions: AKI diagnosed using only the urine output criterion without fulfilling the creatinine criterion and all stages of AKI were associated with long-term mortality. Preoperatively assessed mortality risk using EuroSCORE II did not predict this AKI-associated mortality. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe