The effects of Rituximab on Graves'orbitopathy: A retrospective study of 14 patients.

PURPOSE: Management of Graves' ophthalmopathy remains challenging. Over the last decade, previous studies have shown promising results for Rituximab in the treatment of Graves' ophthalmopathy. We present the response of 14 individuals with active moderate-to-severe Graves' ophthalmopathy to Rituximab, representing one of the largest retrospective case series reported to date. METHODS: Rituximab was administered intravenously, 1000 mg twice at a 2-week interval. The primary end point was a clinical activity score reduction (improvement by ⩾ 2 points or disease inactivation: clinical activity score < 3) at 24 weeks. Secondary end points included clinical activity score improved by ⩾ 2 points or inactivation of Graves' ophthalmopathy at 12 weeks, improvement in each item of the clinical activity score, in proptosis, in severity disease by the total eye score and in diplopia according to the Gorman score. RESULTS: A limited improvement in clinical activity score was observed (median improvement at 24 weeks by 1 point, p = 0.002, (5/14 patients, 35.7%). Disease inactivation occurred in 50% of patients (7/14 patients). At 12 weeks, clinical activity score improved by ⩾ 2 points in 2/14 patients (14.3%) and inactivation of Graves' ophthalmopathy occurred in four patients (28.6%). Improvement in proptosis and total eye score was observed in 3/9 patients (33%) and in 4/14 patients (28.6%) at 24 weeks, respectively. Only one patient experienced moderate adverse event. CONCLUSION: Rituximab is a well-tolerated treatment with a good safety profile, but offered limited and partial improvement for active moderate-to-severe Graves' ophthalmopathy with a long duration of disease.

Perioperative management of adult diabetic patients. Preoperative period.

In diabetic patients undergoing surgery, we recommend assessing glycaemic control preoperatively by assessing glycated haemoglobin (HbA1c) levels and recent capillary blood sugar (glucose) levels, and to adjust any treatments accordingly before surgery, paying particular attention to specific complications of diabetes. Gastroparesis creates a risk of stasis and aspiration of gastric content at induction of anaesthesia requiring the use of a rapid sequence induction technique. Cardiac involvement can be divided into several types. Coronary disease is characterised by silent myocardial ischaemia, present in 30-50% of T2D patients. Diabetic cardiomyopathy is a real cause of heart failure. Finally, cardiac autonomic neuropathy (CAN), although rarely symptomatic, should be investigated because it causes an increased risk of cardiovascular events and a risk of sudden death. Several signs are suggestive of CAN, and confirmation calls for close perioperative surveillance. Chronic diabetic kidney disease (diabetic nephropathy) aggravates the risk of perioperative acute renal failure, and we recommend measurement of the glomerular filtration rate preoperatively. The final step of the consultation concerns the management of antidiabetic therapy. Preoperative glucose infusion is not necessary if the patient is not receiving insulin. Non-insulin drugs are not administered on the morning of the intervention except for metformin, which is not administered from the evening before. The insulins are injected at the usual dose the evening before. The insulin pump is maintained until the patient arrives in the surgical unit. It should be remembered that insulin deficiency in a T1D patient leads to ketoacidosis within a few hours.

Perioperative management of adult diabetic patients. Review of hyperglycaemia: definitions and pathophysiology.

Diabetes mellitus is defined by chronic elevation of blood glucose linked to insulin resistance and/or insulinopaenia. Its diagnosis is based on a fasting blood-glucose level of ≥1.26g/L or, in some countries, a blood glycated haemoglobin (HbA1c) level of >6.5%. Of the several forms of diabetes, type-2 diabetes (T2D) is the most common and is found in patients with other risk factors. In contrast, type-1 diabetes (T1D) is linked to the autoimmune destruction of ß-pancreatic cells, leading to insulinopaenia. Insulin deficiency results in diabetic ketoacidosis within a few hours. 'Pancreatic' diabetes develops from certain pancreatic diseases and may culminate in insulinopaenia. Treatments for T2D include non-insulin based therapies and insulin when other therapies are no longer able to control glycaemic levels. For T1D, treatment depends on long (slow)-acting insulin and ultra-rapid analogues of insulin administered according to a 'basal-bolus' scheme or by continuous subcutaneous delivery of insulin using a pump. For patients presenting with previously undiagnosed dysglycaemia, investigations should determine whether the condition corresponds to pre-existing dysglycaemia or to stress hyperglycaemia. The latter is defined as transient hyperglycaemia in a previously non-diabetic patient that presents with an acute illness or undergoes an invasive procedure. Its severity depends on the type of surgery, the aggressiveness of the procedure and its duration. Stress hyperglycaemia may lead to peripheral insulin resistance and is an independent prognostic factor for morbidity and mortality.

Perioperative management of adult diabetic patients. Intraoperative period.

Perioperative hyperglycaemia (>1.80g/L or 10mmol/L) increases morbidity (particularly due to infection) and mortality. Hypoglycaemia can be managed in the perioperative period by decreasing blood sugar levels with insulin between 0.90 and 1.80g/L but it may occur more frequently when the goal is strict normoglycaemia. We propose continuous administration of insulin therapy via an electronic syringe (IVES) in type-1 diabetes (T1D) and type-2 diabetes (T2D) patients if required or in cases of stress hyperglycaemia. Stopping a personal insulin pump requires immediate follow on with IVES insulin. We recommend 4mg dexamethasone for the prophylaxis of nausea and vomiting, rather than 8mg, combined with another antiemetic drug. The use of regional anaesthesia (RA), when possible, allows for better control of postoperative pain and should be prioritised. Analgesic requirements are higher in patients with poorly controlled blood sugar levels than in those with HbA1c<6.5%. The struggle to prevent hypothermia, the use of RA and multimodal analgesia (which allow for a more rapid recovery of bowel movements), limitation of blood loss, early ambulation and minimally invasive surgery are the preferred measures to regulate perioperative insulin resistance. Finally, diabetes does not change the usual rules of fasting or of antibiotic prophylaxis.

Perioperative management of adult diabetic patients. Specific situations.

Ambulatory surgery can be carried out in diabetic patients. By using a strict organisational and technical approach, the risk of glycaemic imbalance is minimised, allowing the patients to return to their previous way of life more quickly. Taking into account the context of ambulatory surgery, with a same day discharge, the aims are to minimise the changes to antidiabetic treatment, to maintain adequate blood sugar control and to resume oral feeding as quickly as possible. The preoperative evaluation is the same as for a hospitalised patient and recent glycaemic control (HbA1c) is necessary. Perioperative management and the administration of treatment depend on the number of meals missed. The patient can return home after taking up usual feeding and treatment again. Hospitalisation is necessary if significant glycaemic imbalance occurs. In pregnancy, it is necessary to distinguish between known pre-existing diabetes (T1D or T2D) and gestational diabetes, defined as glucose intolerance discovered during pregnancy. During labour, blood sugar levels should be maintained between 0.8 and 1.4g/L (4.4-8.25mmol/L). Control of blood sugar levels is obtained by using a continuous administration of insulin using an electronic syringe (IVES) together with a glucose infusion. Post-partum, management depends on the type of diabetes: in T1D and T2D patients a basal-bolus scheme is restarted with decreased doses while in gestational diabetes insulin therapy is stopped after delivery. Antidiabetic treatment is again necessary if blood sugar levels remain>1.26g/L (7mmol/L).

Perioperative management of adult diabetic patients. Postoperative period.

Follow on from continuous intravenous administration of insulin with an electronic syringe (IVES) is an important element in the postoperative management of a diabetic patient. The basal-bolus scheme is the most suitable taking into account the nutritional supply and variable needs for insulin, reproducing the physiology of a normal pancreas: (i) slow (long-acting) insulin (=basal) which should immediately take over from IVES insulin simulating basal secretion; (ii) ultra-rapid insulin to simulate prandial secretion (=bolus for the meal); and (iii) correction of possible hyperglycaemia with an additional ultra-rapid insulin bolus dose. A number of schemes are proposed to help calculate the dosages for the change from IV insulin to subcutaneous insulin and for the basal-bolus scheme. Postoperative resumption of an insulin pump requires the patient to be autonomous. If this is not the case, then it is mandatory to establish a basal-bolus scheme immediately after stopping IV insulin. Monitoring of blood sugar levels should be continued postoperatively. Hypoglycaemia and severe hyperglycaemia should be investigated. Faced with hypoglycaemia <3.3mmol/L (0.6g/L), glucose should be administered immediately. Faced with hyperglycaemia >16.5mmol/L (3g/L) in a T1D or T2D patient treated with insulin, investigations for ketosis should be undertaken systematically. In T2D patients, unequivocal hyperglycaemia should also call to mind the possibility of diabetic hyperosmolarity (hyperosmolar coma). Finally, the modalities of recommencing previous treatments are described according to the type of hyperglycaemia, renal function and diabetic control preoperatively and during hospitalisation.

Perioperative management of adult diabetic patients. The role of the diabetologist.

A patient should be referred to a diabetologist perioperatively in several circumstances: preoperative recognition of a previously unknown diabetes or detection of glycaemic imbalance (HbA1c <5% or >8%); during hospitalisation, recognition of a previously unknown diabetes, persisting glycaemic imbalance despite treatment or difficulty resuming previously used chronic treatment; postoperatively and after discharge from hospital, for all diabetic patients in whom HbA1c is >8%.