Long-Term Efficacy of Induction Therapy With Anti-Interleukin-2 Receptor Antibodies or Thymoglobulin Compared With No Induction Therapy in Renal Transplantation

Background

Although the utility of antibody induction therapy has been demonstrated in clinical trials, the ideal regimen to use based on patient risk factors has not been fully elucidated. The objectives of this study were to determine the impact of either anti-interleukin-2 receptor antibodies (IL-2RA) or thymoglobulin induction therapies versus no induction therapy on acute rejection rates and on 3-year graft survival rates.

Methods

This retrospective analysis compared 3 patient groups—those who did not receive induction, those who received IL-2RA induction, and those who received thymoglobulin induction.

Results

Three hundred eleven patients were included in this study. Patients were well matched for demographic and immunologic characteristics in the noninduced and IL-2RA induction therapy groups; the thymoglobulin induction group included significantly higher risk patients. The acute rejection rates were significantly lower in the IL-2RA and thymoglobulin groups when compared with the no induction therapy group (28% vs 15% vs 41%, respectively; P = .001), which was confirmed with multivariate analysis. The 3-year graft loss rates (no induction 21% vs IL2-RA induction 19% vs thymoglobulin induction 25%; P > .50) and creatinine concentrations (no induction 1.8 ± 0.7, IL-2RA induction 2.0 ± 1.0, and thymoglobulin induction 1.9 ± 1.2; P = .47) were similar between all groups.

Conclusion

The use of induction therapy significantly reduces the incidence of acute rejection. The use of thymoglobulin induction equalizes 3-year graft survival rates in high-risk patients to those seen in low-risk patients receiving either no induction or IL-2RA induction.     

Should heart,lung, and liver transplant recipients receive immunosuppression induction for kidney transplantation?

Ranney DN, Englesbe MJ, Muhammad W, Al‐Holou SN, Park JM, Pelletier SJ, Punch JD, Lynch RJ. Should heart, lung, and liver transplant recipients receive immunosuppression induction for kidney transplantation?
Clin Transplant 2010: 24: 67–72. © 2009 John Wiley & Sons A/S. Abstract: As the outcomes of heart, liver, and lung transplantation continue to improve, more patients will present for subsequent renal transplantation. It remains unclear whether these patients benefit from induction immunosuppression. We retrospectively reviewed induction on solid organ graft recipients who underwent renal transplant at our center from January 1, 1995 to March 30, 2007. Induction and the non‐induction groups were compared by univariate and Kaplan–Meier analyses. There were 21 patients in each group, with mean follow‐up of 4.5–6.0 years. Forty‐seven percent of patients receiving induction had a severe post‐operative infection, compared with 28.6% in the non‐induction group (p = NS). The one yr rejection rate in the induction group was 9.5% compared with 14.3% for non‐induction (p = NS). One‐yr graft survival was 81.0% and 95.2% in the induction and non‐induction group (p = NS). In summary, there is a trend toward lower patient and graft survival among patients undergoing induction. These trends could relate to selection bias in the decision to prescribe induction immunosuppression, but further study is needed to better define the risks and benefits of antibody‐induction regimens in this population.     

Pretreatment with magnesium sulphate is associated with less succinylcholine-induced fasciculation and subsequent tracheal intubation-induced hemodynamic changes than precurarization with vecuronium during rapid sequence induction

Although it has side effects, succinylcholine is still widely used in rapid sequence induction. The aim of the present study is to evaluate the effects of pretreat ment with magnesium and precurarization of vecuroni um on succinylcholine-induced fasciculation and subse quent tracheal intubation-induced hemodynamic changes during rapid sequence induction. Fifty-five patients were allocated to three groups by a blinded randomization: Group M received saline 100 ml with magnesium 40 mg x kg(-1) for 5 min at 6.5 min before induction and sub sequently administered saline 1-2 ml at 1.5 min before induction; Group V received saline 100 ml for 5 min at 6.5 min before induction and subsequently administered vecuronium 0.02 mg x kg(-1) at 1.5 min before induction; Group C received saline 100 ml for 5 min at 6.5 min before induction and then saline 1-2 ml at 1.5 min before induction. Fasciculation scores and mean percent changes of heart rate, systolic blood pressure and rate pressure product between baseline and after induction were significantly lower in group M than those in group C and group V. Pretreatment with magnesium is more effective to limit succinylcholine-induced fasciculation and subsequent tracheal intubation-induced hemody namic changes in rapid sequence induction compared with vecuronium pretreatment, although magnesium does not prevent the elevation of serum potassium con centration after induction.     

SINGLE BREATH INDUCTION OF ANAESTHESIA WITH ISOFLURANE

This study has compared a single breath induction techniqueand a conventional inhalation induction technique using isofluranein nitrous oxide and oxygen. Each group consisted of 36 unpremedicatedpatients. Single breath induction was associated with fewerproblems on induction, but required more patient co-operation.Ninety-four percent of patients were willing to repeat the singlebreath induction technique, compared with 74% of patients receivinga conventional inhalation induction. ^*Present address, for correspondence: The Sir Humphry Davy Departmentof Anaesthesia, Bristol Royal Infirmary, Bristol BS2 8HW.     

低氧对脂肪间充质干细胞向雪旺细胞分化的影响

目的探讨低氧对脂肪间充质干细胞（ADMSCs）向雪旺细胞（SCs）分化能力的影响。方法分离培养SD大鼠ADMSCs并用流式细胞仪、茜素红染色、油红O染色鉴定。将成功分离的ADMSCs随机分为3组：常氧诱导组,在常氧条件下（5％CO2,21％O2,37℃）诱导;低氧处理＋常氧诱导组,低氧处理（5％CO2,0．5％O2,37℃）后在常氧条件下诱导;低氧诱导组,低氧条件下（5％CO2,0．5％O2,37℃）诱导。观察各组细胞形态,MTT法检测细胞增殖情况,免疫荧光染色和Westernblot检测SCs标志物GFAP和S-100的表达。结果细胞分离后,经流式细胞仪分析可见细胞表面CD44阳性、CD45阳性、CD90阳性,茜素红及油红O染色均为阳性。MTT法检测结果：低氧处理＋常氧诱导组A值为0．861±0．039,高于常氧诱导组0．837±0．017,差异具有统计学意义（P〈0．05）;低氧诱导组A值为0．931±0．041,均高于常氧诱导组和低氧处理＋常氧诱导组（P均〈0．05）。免疫荧光染色发现常氧诱导组和低氧处理＋常氧诱导组大量细胞GFAP和S-100表达阳性,低氧诱导组仅少量细胞S-100和GFAP表达阳性。Westernblot检测发现常氧诱导组S-100蛋白表达最高,低氧处理＋常氧诱导组GFAP蛋白表达最高,低氧诱导组S-100蛋白、GFAP蛋白表达均最低。结论低氧抑制ADMSCs向SCs的分化,低氧处理后的ADMSCs在常氧条件下仍可向SCs分化。     

Anesthetic management of morbidly obese patients using inhalation induction with high concentrations of sevoflurane

We describe successful anesthetic management of three morbidly obese patients, using inhalation induction with high concentrations of sevoflurane. In morbidly obese patients, reduced airway space of the pharynx can cause upper airway obstruction after the induction of general anesthesia and may explain difficult mask ventilation. For these patients, careful airway management is essential during the anesthetic induction. In inhalation induction with sevoflurane, the incidence of transient apnea is lower and the control over depth of anesthesia is easier as compared with intravenous induction. Therefore, sevoflurane may be an excellent induction agent in morbidly obese patients with a potentially difficult airway.     

Assessment of extensive surgery for locally advanced lung cancer. Safety and efficacy of induction therapy.

OBJECTIVE: Locally advanced lung cancer has a poor prognosis, despite extensive surgery conducted in an effort to improve survival. We evaluated the safety and efficacy of induction therapy prior to extensive surgery for locally advanced lung cancer. METHODS: Primary resection for lung cancer was done in 549 consecutive patients divided into three groups; 446 undergoing standard pulmonary resection (no extensive surgery), 87 undergoing extensive surgery without induction therapy, and 16 undergoing surgery after induction therapy. RESULTS: Morbidity was 23.5%, 28.6%, and 43.8%, respectively. The rate was significantly higher in the induction group compared with the no extensive surgery group (P < 0.05). Surgical mortality was 0.67%, 3.4%, and 6.3%, respectively. The difference was statistically significant between the no extensive surgery and extensive surgery groups (P < 0.02), and between the no extensive surgery and induction groups (P < 0.02). Hospital mortality was 2.2%, 9.2%, and 6.3%, respectively. The rates were significantly higher in the extensive surgery (P < 0.01) and induction (P < 0.05) groups compared to the no extensive surgery group. Five-year survival was 50.3% for the patients who received induction therapy, and 14.7% for the patients who did not receive induction therapy. CONCLUSIONS: Survival differences between the induction and non induction groups were not significant, but some patients with T3 or T4 disease may benefit from induction therapy. The high morbidity of induction treatment should be recognized, and strict candidate selection and careful postoperative care used to help prevent increased mortality.     

Induction of labour in Black patients.

The results of a prospective study of induction of labour in 175 Black patients are presented. They show that induction of labour in Blacks, even when performed with optimal care, is more hazardous than in other population groups, owing to an increased proportion of patients of high parity and an increased prevalence of cephalopelvic disproportion. The factors affecting the outcome of induction, the safety of induction and the criteria for a safer induction are discussed.     

Effect of left-to-right, mixed left-to-right, and right-to-left shunts on inhalational anesthetic induction in children: a computer model

We describe a seven-compartment physiologic model of inhalational anesthetic induction with circulatory shunts that was used to simulate inhalational anesthetic induction in children with congenital heart disease. Our conclusions based on this model are that left-to-right (L-R) shunting has little effect on speed of induction; right-to-left (R-L) shunting significantly slows induction of N2O and halothane anesthesia; and adding an L-R shunt to a preexisting R-L shunt will attenuate the slowing of induction caused by the R-L shunt.     

The effect of induction of anesthesia and intubation on end-expiratory lung level and regional ventilation distribution in cardiac children

Background: During the induction of anesthesia, changes in functional residual capacity and ventilation distribution (VD) occur. Although these physiological changes are well investigated in adults, little data are available in infants and children. Aim: To describe continuous changes in lung physiology during the induction of anesthesia in infants and children using electrical impedance tomography (EIT). Methods: Lung mechanics and volume changes in 38 infants and children undergoing elective cardiac surgery were assessed using EIT before, during, and after the induction of anesthesia. End‐expiratory level (EEL as an equivalent to FRC) and VD were measured with EIT and referenced to a period of spontaneous breathing prior to induction. Results: EEL changed significantly during induction with the lowest during the intubation phase and normalized with the application of positive end‐expiratory pressures (PEEP) after induction. Ventilation prior to induction was preferentially distributed toward the dependent lung, whereas after induction, the nondependent lung was better ventilated. PEEP during mechanical ventilation did not improve ventilation inhomogeneity. Conclusion: Lung volume and mechanics deteriorate significantly during the induction of anesthesia and remain altered during mechanical ventilation.     

Non-drug related asystole associated with anaesthetic induction

A patient is presented where routine venepuncture associated with anaesthetic induction resulted in bradycardia and asystole. The case highlights the need for special caution with, and ECG monitoring throughout induction for, patients with a history of syncope. It also demonstrates the need for caution when attributing cardiovascular events during induction to the effect of the induction agents used.     

No induction versus anti-IL2R induction therapy in simultaneous kidney pancreas transplantation: a comparative analysis

The optimal immunosuppressive regimen for simultaneous kidney pancreas transplantation (SKPT) is still not established. We conducted a study to compare the safety and efficacy of no induction versus anti-IL-2 receptor induction protocols in SKPT recipients receiving the same maintenance regimen. METHODS: Sixty-three SKPT recipients were divided into two groups: no induction group (n = 42) and anti-IL-2 receptor induction group (n = 21). All patients were maintained on tacrolimus, mycophenolate mofetil, and prednisone. Primary endpoints were 1-year acute rejection incidence and patient and graft survivals. RESULTS: Demographic characteristics were similar between the groups. Acute rejection incidence at 1 year was equal in both groups (28.6%). Kidney and pancreas allograft survival in the no induction group were 78.6% and 76.2%, and in the anti-IL-2R induction group, 81% and 71.4%, respectively (P = NS). Patient survival was also similar: 83.3% in the no induction versus 85.7% in the anti-IL-2R induction group. Deaths due to sepsis were higher in the anti-IL-2R induction group, albeit not significantly. CONCLUSION: The use of a no-induction protocol in SKPT is safe and effective immunosuppression that also reduces transplantation costs.     

Influence of serum protein,serum albumin concentrations and dose on midazolam anaesthesia induction times

Individual variation occurs in time to induction of anaesthesia with intravenous drugs. Less free drug is available to cross the blood-brain barrier when the drug is highly protein bound. Since this may prolong time to sleep, we correlated the induction time, serum albumin and total protein concentrations, and doses of midazolam, which is a highly protein bound intravenous anaesthetic. There is a poor correlation (r = 0.062) between induction time and serum protein, a weak (r = 0.524) but statistically significant (p = 0.026) correlation between induction time and serum albumin, and a highly significant (p = 0.003) negative correlation (r = -0.579) between drug dose and induction time. The administration of the appropriate dose of midazolam for induction, therefore, appears to affect induction time more significantly than does the serum albumin concentration.     

Comparison of Sevoflurane with Isoflurane for Rapid Mask Induction in Midazolam and Butorphanol‐sedated Dogs

Rapid mask induction can be a useful induction technique for veterinary patients, although it is often accompanied by exaggerated excitement responses in unpremedicated animals (Mutoh et al.: Jpn. J. Vet. Anesth. Surg. 26, 109–116; J. Vet. Med. Sci. 57, 1007–1013; J. Vet. Med. Sci. 57, 1121–1124; 1995). The aim of this study was to compare sevoflurane with isoflurane for rapid mask induction in six dogs sedated by a combination of midazolam (0.1 mg/kg) and butorphanol (0.2 mg/kg). Induction with sevoflurane (5 %, 2.4 minimum alveolar concentration [MAC]) in O₂ resulted in shorter time to loss of the palpebral reflex, negative tail clamp response, and successful intubation than with isoflurane (3 %, 2.4 MAC) in O₂. There were no changes in heart rate or mean arterial blood pressure during induction with sevoflurane, whereas an increase in heart rate was observed in dogs induced with isoflurane. A decrease in respiratory rate compared with the pre‐induction rate was observed during induction, and associated mild respiratory acidosis, characterized by an increase in arterial PCO₂, was measured at the end of the induction period in both induction groups. None of the animals had episodes of induction‐related complications. These results suggest that both sevoflurane and isoflurane produce a smooth onset of induction in midazolam and butorphanol‐sedated dogs. Sevoflurane is a more suitable for rapid mask induction than isoflurane since it provides faster induction associated with a lower blood/gas partition coefficient.     

Assessment of extensive surgery for locally advanced lung cancer

Objective: Locally advanced lung cancer has a poor prognosis, despite extensive surgery conducted in an effort to improve survival. We evaluated the safety and efficacy of induction therapy prior to extensive surgery for locally advanced lung cancer. Methods: Primary resection for lung cancer was done in 549 consecutive patients divided into three groups; 446 undergoing standard pulmonary resection (no extensive surgery), 87 undergoing extensive surgery without induction therapy, and 16 undergoing surgery after induction therapy. Results: Morbidity was 23.5%, 28.6%, and 43.8%, respectively. The rate was significantly higher in the induction group compared with the no extensive surgery group (P < 0.05). Surgical mortality was 0.67%, 3.4%, and 6.3%, respectively. The difference was statistically significant between the no extensive surgery and extensive surgery groups (P < 0.02), and between the no extensive surgery and induction groups (P < 0.02). Hospital mortality was 2.2%, 9.2%, and 6.3%, respectively. The rates were significantly higher in the extensive surgery (P < 0.01) and induction (P < 0.05) groups compared to the no extensive surgery group. Five-year survival was 50.3% for the patients who received induction therapy, and 14.7% for the patients who did not receive induction therapy. Conclusions: Survival differences between the induction and non induction groups were not significant, but some patients with T3 or T4 disease may benefit from induction therapy. The high morbidity of induction treatment should be recognized, and strict candidate selection and careful postoperative care used to help prevent increased mortality.     

Sevoflurane versus propofol for anesthetic induction: a meta-analysis

We performed this meta-analysis to compare the characteristics of sevoflurane and propofol for the induction of routine anesthesia and for laryngeal mask airway (LMA) insertion. The variables assessed were 1) time to loss of consciousness, 2) incidence of apnea during induction, 3) induction complications, 4) time for successful LMA insertion, 5) success with LMA insertion on first attempt, 6) patient dissatisfaction, and 7) postoperative nausea and vomiting. MEDLINE, Embase, and the Cochrane library databases between January 1992 and October 1999 were reviewed for randomized, controlled trials comparing anesthetic induction between sevoflurane/nitrous oxide and propofol. Data from the 12 randomized, controlled studies were used for the meta-analysis. Sevoflurane induction was associated with a trend toward higher patient dissatisfaction and higher first-time success with LMA. Apnea was less common in the sevoflurane group. The incidence of postoperative nausea and vomiting was significantly more frequent in the sevoflurane group (P < 0.05). This effect was still present when all other variables, except the induction methods, were controlled. The other pooled variables did not show a significant difference between sevoflurane and propofol. Sevoflurane and propofol had similar efficacy for anesthetic induction. However, for routine outpatient surgery, propofol may still be the preferred induction anesthetic because of its favorable induction of anesthesia characteristics, high patient satisfaction, and less frequent incidence of postoperative nausea and vomiting. IMPLICATIONS: Sevoflurane and propofol had similar efficacy for anesthetic induction. However, for routine outpatient surgery, propofol may still be the preferred induction anesthetic because of its favorable induction of anesthesia characteristics, high patient satisfaction, and less frequent incidence of postoperative nausea and vomiting.     

Recovery after single-breath halothane induction of anaesthesia in daycase patients

A single-breath technique of inhalational induction of anaesthesia allows intravenous induction agents to be avoided. We have investigated recovery from anaesthesia in 40 daycase patients, using tests of psychomotor function. Patients anaesthetised with inhalational induction awaken earlier than those who receive thiopentone, but not significantly earlier. There were no significant differences in postoperative psychomotor function between patients who received thiopentone and those who had inhalational inductions. Single-breath halothane, nitrous-oxide, oxygen induction is an alternative to intravenous induction in cooperative adults, but does not confer significant benefits in terms of recovery.     

Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation

BACKGROUND: The use of antilymphocyte antibodies for induction therapy or for treatment for rejection has been associated with an increased risk of posttransplant lymphoproliferative disorder (PTLD). The authors investigated the incidence of PTLD after monoclonal antilymphocyte, polyclonal antilymphocyte, interleukin (IL)-2 receptor antibody, or no induction therapy in primary kidney transplant recipients. METHODS: A multivariate Cox analysis of 38,519 primary kidney transplants from January 1, 1997, to December 31, 2000, was performed to compare the incidence of PTLD, graft survival, and patient survival among the induction groups. RESULTS: The actual incidence of PTLD was 0.85% in 2,713 recipients with monoclonal, 0.81% in 4,343 with polyclonal, 0.50% in 7,800 with IL-2, and 0.51% in 23,663 recipients with no induction therapy (P=0.02). The Cox model indicated that as compared with no induction, the increased risk of PTLD was 72% with monoclonal (P=0.03), 29% with polyclonal (P=0.27), and 14% with IL-2 induction (P=0.52). IL-2 receptor antibody was associated with a 17% reduced risk of graft loss (P=0.002) and a 21% reduced risk of mortality (P=0.005) compared with no induction. Monoclonal and polyclonal induction therapies were not associated with a reduced risk of graft loss or mortality. Mycophenolate mofetil discharge maintenance immunosuppression was associated with a significantly reduced risk of PTLD and graft loss compared with azathioprine. CONCLUSIONS: Among induction therapies, IL-2 receptor antibody induction was associated with the smallest risk of PTLD and improved graft and patient survival. Monoclonal or polyclonal induction was not associated with improved graft or patient survival, and monoclonal induction was associated with an increased risk of PTLD.     

Induction with sevoflurane-remifentanil is comparable to propofol-fentanyl-rocuronium in PONV after laparoscopic surgery

PURPOSE: To compare sevoflurane-remifentanil induction and propofol-fentanyl-rocuronium induction with regards to the frequency of moderate to severe postoperative nausea and vomiting (PONV) in the first 24 hr after laparoscopic day surgery. METHODS: After informed consent, 156 ASA physical status class I to III patients undergoing laparoscopic cholecystectomy or tubal ligation were randomized to either induction with sevoflurane 8%, N(2)O 67% and iv remifentanil 1 to 1.5 microg.kg(-1) or induction with iv fentanyl 2 to 3 microg.kg(-1), propofol 2 mg.kg(-1), and rocuronium 0.3 to 0.5 mg.kg(-1). All patients received iv ketorolac 0.5 mg.kg(-1) at induction and sevoflurane-N(2)O maintenance anesthesia with rocuronium as needed. PONV was treated with iv ondansetron, droperidol, or dimenhydrinate; postoperative pain was treated with opioid analgesics. Patients were followed for 24 hr with regards to PONV and pain. Intubating conditions, induction and emergence times, time to achieve fast-track discharge criteria, and drug costs were measured. RESULTS: No differences were seen between the two groups in their frequencies of 24-hr moderate to severe PONV and postoperative pain, or in their intubating conditions, induction and emergence times, and time to achieve fast-track discharge criteria. Patients undergoing sevoflurane-remifentanil induction received more morphine (11 mg vs 8 mg; P < 0.001) in the postanesthetic care unit. Sevoflurane-remifentanil induction resulted in similar anesthetic and total drug costs for both procedures. CONCLUSION: We did not demonstrate any difference in PONV, pain, or anesthetic/recovery times or costs between the sevoflurane and propofol groups. Sevoflurane-remifentanil induction is a feasible technique for anesthetic induction.     

Perioperative anxiety and postoperative behavioural disturbances in children undergoing intravenous or inhalation induction of anaesthesia

BACKGROUND: There are few published data comparing the psychological effects of intravenous (i.v.) and inhalation methods of anaesthesia induction in children. In the present study, we compared perioperative anxiety and postoperative behavioural changes in children undergoing standardized i.v. induction with thiopental and inhalation induction with sevoflurane for routine ear, nose and throat surgery. METHODS: Children were randomly assigned to receive inhalation induction with sevoflurane or i.v. induction with thiopental. Anxiety was assessed on arrival, at induction and 30 min after transfer to the recovery room using a four-point scale. The incidence of postoperative behavioural disturbances was determined using a postoperative questionnaire. RESULTS: Significantly more children were anxious during induction in the i.v. group than in the inhalation group [23 of 50 (46%) versus 5 of 50 (10%); P = 0.0001]. Mean induction time was shorter (5.6 versus 7.0 min; P = 0.0001) and recovery time longer (30.5 versus 10.4 min; P = 0.0001) in the i.v. group compared with the inhalation group. Problematic behavioural changes were reported in the first 2 weeks after surgery in nine of 32 children (28%) in the i.v. group and 16 of 34 (48%) children in the inhalation group (P = 0.13). CONCLUSIONS: Although children were more anxious during i.v. induction than inhalation induction, there was no difference in the incidence of behavioural disturbances in the first 2 weeks postoperatively.