Contingency Plan for the Intensive Care Services for the COVID-19 pandemic. / Plan de contingencia para los servicios de medicina intensiva frente a la pandemia COVID-19.

In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC, have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.

[EVALUATION OF SEDATION USING THE RICHMOND AGITATION SEDATION SCALE IN PATIENTS WITH PROLONGED MECHANICAL VENTILATION]. / Evaluación de la sedación mediante la escala Richmond Agitation Sedation Scale. EN PACIENTES CON VENTILACIÓN MECÁNICA DE LARGA DURACIÓN.

INTRODUCTION: Sedation is monitored to avoid both under- and oversedation. OBJECTIVES: Determine the most prevalent sedation levels in the ICU according to RASS categories and whether treatment is individualized on the basis of these scores. METHODS: Prospective cohort study of patients connected to mechanical ventilation ≥ 96 hours in the intensive care unit between January 1 and August 31. Daily assessments were recorded in the intensive care unit, together with sedoanalgesic treatment, ventilation modes, or vital signs. RESULTS: We analyzed 1021 RASS scores collected over a total of 220 MV days, categorized in the following ranges: 404 (39.6%) deep sedation, 474 (46.4%) conscious sedation, and 54 (5.3%) agitation; 89 (8.7%) were missing scores. Patients receiving continuous sedoanalgesia were more likely to be in the deep sedation than conscious sedation range (87.1% vs. 32.3%, p < 0.001). Analysis of patients under continuous sedation and in ventilation mode found more changes in the conscious sedation range than in deep sedation (42.5% vs. 22.3% and 12.6% vs. 2.9%, respectively; p < 0.001 in both cases). In conscious sedation range there was increased use of opiates in bolus (6.4%). CONCLUSIONS: Deep sedation was clearly prevalent in patients with mechanical ventilation under continuous sedation, with few changes in ventilation mode, because it is prevalent control ventilation mode and no changes in sedonalagesic perfusion in that range.

Optimal insulin treatment in syngeneic islet transplantation.

Insulin-induced normoglycemia has shown to have a beneficial effect on the outcome of pancreatic islets transplanted to diabetic recipients. The aim of the study was to identify the insulin treatment that can maximize its beneficial effect on islet transplants. Six groups of streptozotocin diabetic C57Bl/6 mice were transplanted (Tx) with 100 syngeneic islets, an insufficient beta cell mass to restore normoglycemia, and were treated with insulin as follows: group 1 (n = 9): from day 10 before Tx to day 14 after Tx; group 2 (n = 11): from day 6 before Tx to Tx day; group 3 (n = 11): from Tx day to day 6 after Tx; group 4 (n = 7): from Tx day to day 14 after Tx; group 5 (n = 8): from day 10 to day 24 after Tx; group 6 (n = 18): Tx mice were not treated with insulin. Sixty days after Tx, normoglycemia was achieved in 100% of mice in groups 1, 4, and 5, in 73% of mice in group 2, and in only 45% and 33% of mice in groups 3 and 6, respectively (p < 0.01). Intraperitoneal glucose tolerance, determined only in normoglycemic mice, was similar in groups 1, 2, 4, and normal controls. In contrast, normoglycemic mice from groups 3, 5, and 6, exposed to more severe and prolonged hyperglycemia after Tx, showed higher glucose values after glucose injection, suggesting that hyperglycemia had a long-lasting deleterious effect on transplanted beta cell function. The initially transplanted beta cell mass was maintained in the grafts of normoglycemic mice, but was severely reduced in hyperglycemic mice. Transplanted beta cell mass was similar in normoglycemic groups with normal or impaired glucose tolerance, indicating that impaired glucose tolerance was not due to reduced beta cell mass. In summary, the beneficial effect of insulin-induced normoglycemia on transplanted islets was maximal when insulin treatment was maintained the initial 14 days after transplantation. Exposure to sustained hyperglycemia initially after transplantation had a long-lasting deleterious effect on transplanted islets.

Mechanisms of glucose hypersensitivity in beta-cells from normoglycemic, partially pancreatectomized mice.

Increased beta-cell sensitivity to glucose precedes the loss of glucose-induced insulin secretion in diabetic animals. Changes at the level of beta-cell glucose sensor have been described in these situations, but it is not clear whether they fully account for the increased insulin secretion. Using a euglycemic-normolipidemic 60% pancreatectomized (60%-Px) mouse model, we have studied the ionic mechanisms responsible for increased beta-cell glucose sensitivity. Two weeks after Px (Px14 group), Px mice maintained normoglycemia with a reduced beta-cell mass (0.88 +/- 0.18 mg) compared with control mice (1.41 +/- 0.21 mg). At this stage, the dose-response curve for glucose-induced insulin release showed a significant displacement to the left (P < 0.001). Islets from the Px14 group showed oscillatory electrical activity and cytosolic Ca2+ ([Ca2+]i) oscillations in response to glucose concentrations of 5.6 mmol/l compared with islets from the control group at 11.1 mmol/l. All the above changes were fully reversible both in vitro (after 48-h culture of islets from the Px14 group) and in vivo (after regeneration of beta-cell mass in islets studied 60 days after Px). No significant differences in the input resistance and ATP inhibition of ATP-sensitive K+ (K(ATP)) channels were found between beta-cells from the Px14 and control groups. The dose-response curve for glucose-induced MTT (C,N-diphenyl-N''-4,5-dimethyl thiazol 2 yl tetrazolium bromide) reduction showed a significant displacement to the left in islets from the Px14 group (P < 0.001). These results indicate that increased glucose sensitivity in terms of insulin secretion and Ca2+ signaling was not due to intrinsic modifications of K(ATP) channel properties, and suggest that the changes are most likely to be found in the glucose metabolism.

Normoglycemia restores beta-cell replicative response to glucose in transplanted islets exposed to chronic hyperglycemia.

We studied the effects of chronic hyperglycemia on beta-cell replication and mass in transplanted (Tx) islets. Five groups of streptozocin-induced diabetic C57Bl/6 mice were transplanted with 100 (Tx-100) syngeneic islets, an insufficient beta-cell mass to restore normoglycemia. Groups 1 and 2 remained hyperglycemic throughout the study; after 30 days of hyperglycemia, a second transplantation of 250 islets (Tx-250) restored normoglycemia in groups 3, 4, and 5. Tx-250 was harvested on day 60 in all three groups, and transient mild hyperglycemia developed (10-12 days); thereafter, Tx-100 maintained blood glucose values in the normal range. Tx-100 was harvested 14 (group 1), 60 (groups 2 and 3), 74 (group 4), and 90 (group 5) days after transplantation. Hyperglycemia increased beta-cell replication after 14 days (group 1: 1.26 +/- 0.18%, P < 0.05) but not after 60 days (group 2: 0.59 +/- 0.13%) compared with islets exposed to normoglycemia (group 3: 0.51 +/- 0.07%) (analysis of variance [ANOVA], P < 0.0002). beta-cell replication in group 4 increased after Tx-250 harvesting (0.94 +/- 0.16%, P < 0.05). The initially Tx beta-cell mass (0.21 +/- 0.014 mg) was progressively reduced in hyperglycemic groups (group 1: 0.13 +/- 0.020 mg; group 2: 0.048 +/- 0.012 mg; P < 0.05) (ANOVA, P = 0.0001). Restoration of normoglycemia after Tx-250 did not modify beta-cell mass in Tx-100 grafts (group 3: 0.076 +/- 0.008 mg). However, after Tx-250 harvesting, beta-cell mass increased progressively (group 4: 0.11 +/- 0.018 mg; group 5: 0.14 +/- 0.026 mg, P < 0.05), although it was still reduced compared with the initially Tx beta-cell mass (P < 0.05). In summary, Tx islets exposed to severe chronic hyperglycemia showed a limited beta-cell replication and a progressive reduction in beta-cell mass. With normoglycemia, the Tx beta-cells recovered the replicative response to glucose and partially restored the initially Tx beta-cell mass, indicating that normoglycemia, even after long-term hyperglycemia, has a beneficial effect in islet transplantation.

Improved outcome of islet transplantation in insulin-treated diabetic mice: effects on beta-cell mass and function.

Insulin treatment may improve the outcome of islet transplantation. To determine the effects of insulin treatment on transplanted islets, 4 groups of streptozotocin-diabetic C57BL/6 mice were transplanted with 100 islets, an insufficient beta-cell mass to restore normoglycaemia. Groups 1 (n = 12) and 2 (n = 12), were kept normoglycaemic with insulin treatment from day 10 before transplantation to day 14 after transplantation; groups 3 (n = 12) and 4 (n = 18), were not treated with insulin. Grafts were harvested 14 (groups 1 and 3) or 60 (groups 2 and 4) days after transplantation and beta-cell mass and replication were measured. When insulin was discontinued all mice maintained normoglycaemia; in contrast, non-insulin-treated groups remained hyperglycaemic throughout the study. Fourteen days after transplantation the beta-cell mass was reduced both in group 1 (0.09 +/- 0.01 mg) and group 3 (0.14 +/- 0.02 mg) compared to the initially transplanted mass (0.22 +/- 0.02 mg, p < 0.01); beta-cell replication and area did not change in group 1, but were increased in group 3. Insulin content, expressed as a function of beta-cell mass, was maintained in group 1 grafts (12.5 +/- 2.0 micrograms/mg), but was severely reduced in group 3 (1.0 +/- 0.2 micrograms/mg) compared to non-transplanted islets (20.4 +/- 3.3 micrograms/mg). In group 2, beta-cell mass increased when insulin was discontinued; 60 days after transplantation beta-cell mass was similar to the initially transplanted mass (0.23 +/- 0.04 mg), glucose levels after an intraperitoneal glucose challenge were normal, and insulin content was preserved (19.6 +/- 2.7 micrograms/mg). In contrast, beta-cell mass was progressively reduced in group 4 (0.08 +/- 0.02 mg, p < 0.001). In summary, insulin treatment reduced the beta-cell mass needed to achieve normoglycaemia in islet transplantation. Islets transplanted to insulin-treated mice showed better beta-cell function, preserved insulin content, and were able to increase their beta-cell mass to meet an increased functional demand.

Beta-cell growth and mass are preserved in long-term syngeneic islet transplantation in streptozocin-induced diabetic Lewis rats.

We determined beta-cell replication and mass in basal and stimulated conditions in long-term transplanted islets. Three groups of streptozocin-induced diabetic Lewis rats were transplanted with 1,000 islets (500 islets under left and right kidney capsules). At 2 (Tx-2), 5 (Tx-5), or 9 (Tx-9) months after transplantation, one of the two grafts (basal) was harvested; 14 days later, the contralateral graft (stimulated) was also harvested. Normoglycemia was achieved and maintained in all transplanted rats, although the capacity to respond to a glucose challenge deteriorated slightly 9 months after transplantation. Beta-cell replication remained stable in Tx-2, Tx-5, and Tx-9 basal grafts and was similar to replication in a control group of nontransplanted rats (0.28 +/- 0.06%); replication increased in Tx-2 (0.90 +/- 0.23%, P < 0.05) and Tx-9 (0.72 +/- 0.09%, P < 0.05) stimulated grafts. Beta-cell mass in basal grafts was similar to the initially transplanted mass (1.24 +/- 0.06 mg) and increased in stimulated grafts in Tx-2 (1.91 +/- 0.38 mg, P < 0.05) and Tx-5 (1.73 +/- 0.27 mg, P = 0.01) groups, compared with basal grafts, and in Tx-2 and Tx-9 groups (1.92 +/- 0.30 mg, P < 0.05), compared with initially transplanted mass. Therefore, beta-cell replication and mass were preserved up to 9 months after syngeneic transplantation, and beta-cells maintained the capacity to respond to increased metabolic demand, suggesting that replication is not a limiting factor in the survival of transplanted islets.