Adequate trial

Compared with patients who did not use PGE1, patients in Group C had comparable complications and lung infection scores. Peer Review reports. Open radical esophagectomy with extended lymph node dissection is vital for treating esophageal cancer EC , whether EC is early and locally advanced [ 1 , 2 ].

One-lung ventilation OLV has been extensively used throughout thoracic surgery, being conducive to surgical exposure [ 3 ]. However, OLV can decrease the partial pressure of arterial oxygen PaO 2 and lead to hypoxemia by increasing intrapulmonary shunts and alveolar death space [ 4 , 5 ].

Furthermore, it has been reported that hypoxemia is associated with an increased risk of complications, such as cognitive impairment, atrial fibrillation, renal failure, and pulmonary hypertension [ 6 , 7 ].

Therefore, the prevention and treatment of hypoxemia during OLV is an essential part in intraoperative anesthesia management. A high fraction of inspiration O 2 FiO 2 has been usually adopted to prevent hypoxemia in clinical practice [ 8 ]. According to current protective ventilation strategies, the FiO 2 should be controlled to the lowest level in the case of sufficient oxygenation, without specific reference of FiO 2 concentrations [ 10 ].

Patients with EC scheduled to undergo selective open radical resection were recruited from Affiliated Cancer Hospital of Nanjing Medical University between and Diagnosis of EC patients was based on clinical, laboratory, histopathological, and gastroscopy assessment. Random number table was used for group assignment Fig.

This randomized controlled clinical trial was registered at chictr. After completing pre-operation preparation, all participants underwent general anesthesia and intubation with a left-side double-lumen tube DLT. Thirty minutes before admission to the operating room, patients received phenobarbital 0.

A central venous catheter was inserted via the right internal jugular vein. Midazolam 0. A left-side DLT was then inserted, with fiber bronchoscopy being used to confirm its position. The unventilated lungs were directly connected to the room air. Depth of anesthesia was monitored by the bispectral index BIS , keeping it between 40 and After confirming the placement of a DLT with a fiberoptic bronchoscope, the patient was repositioned to a right lateral decubitus position, and double lungs were ventilated to nebulization.

The Yuyue A ultrasonic nebulizer was modified in 2 steps: firstly, seal the bottom of the sprayer tank to remove the air inlet; secondly, isolate the two original atomizer outlets to ensure that one of the exits was a new intake, and the other was the only outlet towards the patients. The device was then connected to the designated breathing circuit [ 16 ].

Shunt fraction was calculated using the following formula:. Venous blood sampling through the central line was collected at T1, T5, 30 min after restarting two-lung ventilation TLV T7 and 24 h after surgery T8. Clinical pulmonary infection score CPIS [ 19 ], complications pleural effusion, pneumothorax, anastomotic leakage and incision infection , length of stay in the hospital or ICU, and the grade of wound healing were used as our prognostic indicators.

All data analyses were performed by R4. At least 24 patients were required in each group to achieve a power of 0. Counting data was tested by the chi-square test. A total of 90 patients [71 No patient developed hypoxemia among the two groups.

Table 2 shows the clinical characteristics of all the patients. Data acquired at each time point were statistically analyzed using analysis of variance. Data of inflammatory factors collected at each time point were compared by analysis of variance. In addition, there was no significant difference in lung infection scores, complications, length of stay in hospital and ICU, and grade of wound healing between patients in Group C and those who did not use PGE1 Table 6.

Inhaling PEG1, a kind of selective pulmonary artery dilator, by ultrasonic atomization during OLV could dilate the pulmonary artery, which causes stealing blood from the shunt area to the non-shunt area, reducing intrapulmonary shunt [ 21 , 22 ]. This may be because pre-nebulization of PGE1 to the ventilated lung of OLV during two-lung ventilation could reduce shunt and improve oxygenation.

The mechanisms may be multifaceted. It has been proved experimentally that hypoxic pulmonary vasoconstriction HPV could improve oxygenation function in vivo by reducing intrapulmonary shunt [ 23 , 24 ].

In addition, we found that patients receiving 0. Previous research exhibited that MDA levels were indirect indicators of oxidative stress, and MDA was associated with lung injury [ 25 ]. This study further found that 0. Nevertheless, several limitations in this study could not be ignored. Firstly, further subgroup analysis based on complications, age, or gender was unable to be performed due to the small sample size.

Secondly, participants with pulmonary dysfunction were not be enrolled in this study. Thirdly, we used ScvO 2 instead of SvO 2 in the calculation of shunt fraction. ScvO 2 measures the oxygen saturation of the superior vena cava, while SvO 2 measures the oxygen saturation of the whole body, including the abdomen and lower extremities, so the absolute value is different.

Using ScvO 2 to estimate SvO 2 in calculating the shunt fraction was imperfect, and ScvO 2 depended on catheter placement, patient anatomy and physiological state [ 17 ]. Fourthly, we speculated that pre-nebulization of PGE1 to the ventilated lung of OLV during two-lung ventilation could reduce shunt and improve oxygenation, but FiO 2 changes may also have an impact on the shunt.

Based on the existing results in this article, we are not sure whether the reduction in the shunt fraction is affected by PGE1. More rigorously designed prospective researches with larger sample sizes are required to confirm our results. For example, the investigators state:. Consequently, the outcomes in this report may exceed those that are presently obtained in daily practice wherein neither symptoms nor side-effects are consistently measured and wherein practitioners vary greatly in the timing and level of dosing [emphases added].

Only then will the lessons learned from this once-in-a-generation study be fully known and made available to inform clinical practice and guide subsequent research efforts to improve on the same. He also owns stock options in CNS Response, a company that markets a quantitative electroencephalogram database to predict medication response, and is a partner in Positive Brain Training, LLC, a neurofeedback practice.

References 22 and 23 can be found in eTable 1. National Center for Biotechnology Information , U. Journal List Can J Psychiatry v. Can J Psychiatry. H Edmund Pigott , PhD 1. Find articles by H Edmund Pigott. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC.

Open in a separate window. Figure 1. Figure 2. For example, the investigators state: high quality of care was delivered measurement-based care. Click here to view. References 1. Am J Psychiatry. Psychiatr Clin North Am. N Engl J Med. Medication augmentation after the failure of SSRIs for depression. Jul 31, [date cited unknown]. Google Scholar.

Sleep in autism spectrum disorders. Current Sleep Medicine Reports, 1 2 , — Waldhauser, F. Alterations in nocturnal serum melatonin levels in humans with growth and aging. Wright, B. Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: A randomised controlled crossover trial. Wu, Z. Autism spectrum disorder ASD : Disturbance of the melatonin system and its implications.

Yuge, K. Long-term melatonin treatment for the sleep problems and aberrant behaviors of children with neurodevelopmental disorders. BMC Psychiatry, 20 1 , Download references. The authors are grateful to all investigators and subinvestigators, and clinical research coordinators at respective medical institutions for child recruitment, data acquisition, and study conduct, to children along with their families for their participation in the present study, and to Satoshi Sakima, MD, for valuable discussions about the manuscript; his effort was compensated by Nobelpharma Co.

You can also search for this author in PubMed Google Scholar. MH and KM conceived the study. IH made the analyses. MH prepared the first draft of the manuscript.

MH and KM finalized the manuscript. All authors edited and contributed to the final version of the manuscript and gave final approval to the submitted version. Correspondence to Masaharu Hayashi. MH reported receiving consulting fees from Nobelpharma during the conduct of the study. MF reported receiving grant support from Nobelpharma.

YY reported receiving grant support from Nobelpharma. Nobelpharma Co. This study was performed in accordance with the Declaration of Helsinki.

Ethical approval was obtained from the institutional review board at each participating institution. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions. Hayashi, M. J Autism Dev Disord Download citation. Accepted : 07 June Published : 28 June Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search SpringerLink Search. Abstract Robust clinical evidence has not been available for melatonin, a drug commonly administered for treating sleep problems of children with autism spectrum disorder ASD.

References Abdelgadir, I. Google Scholar Veatch, O. Acknowledgments The authors are grateful to all investigators and subinvestigators, and clinical research coordinators at respective medical institutions for child recruitment, data acquisition, and study conduct, to children along with their families for their participation in the present study, and to Satoshi Sakima, MD, for valuable discussions about the manuscript; his effort was compensated by Nobelpharma Co.

Funding The present study was funded by Nobelpharma Co. Author information Author notes Masaharu Hayashi and Kazuo Mishima are contributed equally to this study. View author publications. Ethical Approval This study was performed in accordance with the Declaration of Helsinki. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information.