There is no reliable and safe method for measuring plasma volume in ill newborn infants. We describe an adaptation of the dye dilution technique using indocyanine green as the plasma label, which can be used in the sickest and smallest of infants with the minimum of disturbance. To avoid the need to take large volumes of blood from the infant, samples were diluted 1:1 with distilled water and pooled adult sera was used to construct the dye dilution standard curves. Eighteen preterm and fullterm infants were studied on 30 occasions. The measured plasma volume ranged between 21-4 and 106 ml/kg. Paired measurements were performed within 30-90 minutes of each other in seven infants. In five infants estimations of plasma volume were made shortly before and 30 minutes after the infusion of a known quantity of plasma. In eight out of 12 infants who had two measurements made there was close agreement between the second measured volume and the first measured volume, taking into account how much plasma had been given to or taken from the infant between the two measurements. The error ranged from 0-2 to 5-2 ml and the plasma recovery error ranged from -2-9% to +4-7%. In the remaining four infants the errors ranged from 2-1 to 9-5 ml and -14-2% to +8-8%. Errors in the measurement of plasma volume may arise as the result of sampling too early before full mixing of the dye has occurred, and there is a potential error in the measurement due to the distribution of albumin in the extracellular space in sick infants resulting in an overestimation of the plasma volume. Proposals for reducing sources of errors are discussed.

Neonatal respiratory distress syndrome EDITOR,-Professor Southall and colleagues' question the comments of the working group on the management of neonatal respiratory distress syndrome regarding parameters of oxygenation.2 We write in support of the provisional and practical suggestion of an arterial oxygen saturation (Sao2) range of 85-93% and suggest that much of the data quoted by Southall et al is not applicable to this clinical setting.Professor Southall and colleagues suggest an upper limit for Sao2 of 96% and quote four studies in support of this choice. In two of these papers,3 4 the majority of the patients were not preterm and were receiving treatment for other conditions, mainly congenital heart disease. These infants constitute a very different population from those suffering from respiratory distress syndrome. Our own study of 477 measurements made in clinical practice using Ohmeda Biox oximeters on a population under 33 weeks' gestation found that if the saturation value was 93% or below the arterial oxygen tension (Pao2) was never greater than 12 kPa. Our recommended lower limit for saturation was originally based on a study of 'well' preterm infants at discharge from hospital. It has now been confirmed in a study of nondistressed preterm neonates investigated during their first week of life.4 It does not seem unreasonable to aim to achieve the same range of Sao2 in 'sick' preterm infants. The argument that the latter group had recently experienced a physiological intrauterine PaQ2 of 4-5-6-0 In 31 infants the mean arterial blood pressure (MABP) was measured by invasive arterial methods. Blood volume was assessed using an indocyanin green dye dilution method described previously in this age group.2 The infants had a median gestational age of 26 weeks (range 25-31 weeks) and a median birth weight of 900 g (range 580-1380 g). Readings were all obtained in the first three days of life.The median blood volume observed in our infants was 85 ml/kg (range 46-131 ml/kg), very similar to both the 83 ml/kg of Bauer et al and to previously published data. We found a median MABP of 36 mm Hg (range 18-47). We found no significant relationship, on regression analysis, between observed blood volume and MABP, p=0-42 (figure).

No abstract

Two guidelines about opioid use in chronic pain management were published in 2017: the Canadian Guideline for Opioids for Chronic Non-Cancer Pain and the European Pain Federation position paper on appropriate opioid use in chronic pain management. Though the target populations for the guidelines are the same, their recommendations differ depending on their purpose. The intent of the Canadian guideline is to reduce the incidence of serious adverse effects. Its goal was therefore to set limits on the use of opioids. In contrast, the European Pain Federation position paper is meant to promote safe and appropriate opioid use for chronic pain.     The content of the two guidelines could have unintentional consequences on other populations that receive opioid therapy for symptom management, such as patients with cancer. In this article, we present expert opinion about those chronic pain management guidelines and their impact on patients with cancer diagnoses, especially those with histories of substance use disorder and psychiatric conditions. Though some principles of chronic pain management can be extrapolated, we recommend that guidelines for cancer pain management should be developed using empirical data primarily from patients with cancer who are receiving opioid therapy.

No abstract

No abstract

No abstract

e15180 Background: ZOL therapy is associated with severe (i.e., grade ≥ 3) hypocalcemia and hypophosphatemia in a subset of patients with metastatic CRPC. However, as opposed to the distinct clinical picture of hypocalcemia, the symptoms of hypophosphatemia are less pathognomonic. Furthermore, serum phosphate abnormalities are not regularly reported. Methods: To characterize the rate and clinical impact of severe hypophosphatemia in CRPC patients undergoing ZOL therapy, we identified CRPC patients receiving at least 3 doses of ZOL at our Centre between 01/2004 and 03/2011. Patient demographics, disease characteristics and laboratory parameters were extracted using the Oncology Symptom Control and Information Resource database, and by means of manual chart review. Results: 12 of 90 evaluable patients developed grade ≥ 3 hypophosphatemia (nadir) after 364±299 days (mean±SD) following the first dose of ZOL. While only one patient presented with concomitant severe hypocalcemia, the hypophosphatemia nadir coincided with rising PSA readings in 9 out of 11 informative patients. Severe ZOL-associated hypophosphatemia identified patients with worse outcome (median overall survival from time of CRPC diagnosis to death 685 days) compared to patients without documented hypophosphatemia (907 days, HR 0.52, p=0.049; n=42), or patients with grade 1-2 hypophosphatemia (1035 days, HR 0.44, p=0.016; n=36). Otherwise, the prognostic nomogram developed by Armstrong et al appears not to capture the poor prognosis of patients with severe ZOL-associated hypophosphatemia. Conclusions: Grade 3-4 hypophosphatemia occurs in about 15% of CRPC patients undergoing ZOL therapy and is associated with worse prognosis when compared to patients with absent or mild hypophosphatemia. The latter is usually transient and likely related to increased parathyroid hormone levels due to calcium decreases as a consequence of bisphosphonate therapy. On the other hand, the distinct clinical behavior of CRPC presenting with ZOL-associated severe hypophosphatemia suggests that secreted tumor-associated factors such as fibroblast growth factor 23 may contribute to this phenomenon.