Safety and efficacy of two protocols for sedation in pediatric oncology procedures

Invasive procedures, such as the lumbar puncture, can cause anxiety and pain in children undergoing treatment for acute lymphoblastic leukemia (ALL). We investigated the safety and efficacy of two different protocols for pain relief in 20 children with ALL undergoing lumbar puncture. Protocol A was composed of an association between propofol and alfentanil. Protocol B consisted in the combination of propofol and ketamine. Vital and behavioural parameters, sedation and pain scores were recorded at different times during and after the procedure. All patients showed a satisfactory sedation and analgesia. We found a statistically significant difference of vital parameters between protocol A and protocol B, while there were no significative differences between sedation scores and the other parameters evaluated. Patients in protocol A showed a higher incidence of major side effects, such as respiratory depression. Our results show that both protocols are effective to obtain a good sedation and analgesia in children with ALL undergoing lumbar puncture, but the association between propofol and ketamine appears more safe due to the lower incidence of side effects.     

Sedation and analgesia in the intensive care unit: evaluating the role of dexmedetomidine.

PURPOSE: A review highlighting the application of sedatives and analgesics in the intensive care unit (ICU) setting, with a focus on the use of dexmedetomidine, is presented. SUMMARY: Relevant and applicable clinical trials that resulted from a search of the literature from 1966 to July 2006 using key search terms such as dexmedetomidine, intensive care unit, sedation, delirium, and analgesia were evaluated. Many agents have been evaluated in the search of the optimal regimen for sedation and analgesia in the ICU, including opioids, benzodiazepines, propofol, and antipsychotic agents. Dexmedetomidine has demonstrated efficacy as a sedative analgesic on the basis of its ability to lower opioid, benzodiazepine, and propofol requirements in clinical trials. The role of dexmedetomidine in ICU clinical practice is limited because of a lack of mortality and other morbidity endpoints, such as ICU length of stay, hospital length of stay, time to extubation, long-term complications after discharge from the ICU, and delirium. The most commonly reported adverse effects of dexmedetomidine are secondary to its effects as an alpha(2)-receptor agonist and are cardiac in nature. A detailed cost analysis may be warranted to justify the relatively high acquisition cost of dexmedetomidine. CONCLUSION: Dexmedetomidine may be an effective agent for ICU sedation and analgesia. However, the lack of clinically relevant endpoints in trials, the concern about adverse cardiovascular effects, and the relatively high acquisition cost of this drug limit its use to a select number of patients who may benefit from its distinguished mechanism of action.     

Remimazolam: Pharmacologic Considerations and Clinical Role in Anesthesiology

Midazolam, fentanyl, and propofol are commonly used for sedation in modern anesthesia practice. These agents possess characteristics that have afforded various anesthetics to be delivered and produce relatively safe and effective outcomes. However, each agent has certain drawbacks in clinical practice. Remimazolam, a novel benzodiazepine created out of so‐called soft drug development, is an ultrashort‐acting intravenous sedative‐hypnotic currently being investigated in clinical trials. In this review, we evaluate the recent literature on the use of remimazolam in clinical practice as compared with current sedative agents, and we describe its potential roles for use in sedation. A literature search of the Medline database (2012–May 2016) was performed. Additional references were identified from a review of literature citations, manufacturer reports, and professional meeting abstracts. All premarket studies involving remimazolam as the primary study drug were evaluated. Literature describing the pharmacokinetics and pharmacodynamics of remimazolam, propofol, and midazolam was also included. Phase I and II studies in the United States have shown remimazolam to be a safe and effective option for procedural sedation. Unlike midazolam and propofol, remimazolam undergoes organ‐independent metabolism to an inactive metabolite. Because remimazolam follows first‐order pharmacokinetics, prolonged infusions or higher doses are unlikely to result in accumulation and extended effect, making it favorable for use as an intravenous anesthetic and for sedation in the intensive care unit. It is expected that phase III trials will further describe the niche that remimazolam may be able to occupy in clinical practice. Postmarket cost‐benefit analyses will need to be performed.     

Emergency department management of pain and anxiety related to orthopedic fracture care: a guide to analgesic techniques and procedural sedation in children

Orthopedic fractures and joint dislocations are among the most painful pediatric emergencies. Safe and effective management of fracture-related pain and anxiety in the emergency department reduces patient distress during initial evaluation and often allows definitive management of the fracture. No consensus exists on which pharmacologic regimens for procedural sedation/analgesia are safest and most effective. For some children, control of fracture pain is the primary goal, whereas for others, relief from anxiety is an additionally important objective. Furthermore, strategies for the management of fracture pain may vary by fracture location and patient characteristics; thus, no single regimen is likely to provide the best means of analgesia and anxiolysis for all patients. Effective analgesia can be provided by local or regional anesthesia, such as hematoma, Bier, or nerve blocks. Alternatively, induction of deep sedation with analgesic agents such as ketamine or fentanyl, often combined with sedative-anxiolytic agents such as midazolam, may be used to manage distress associated with fracture reduction. A combination of local anesthesia with moderate sedation, for example nitrous oxide, is another attractive option.     

Adverse Events Associated With Procedural Sedation in Pediatric Patients in the Emergency Department

Purpose:

To determine the agents used by emergency medicine (EM) physicians in pediatric procedural sedation and the associated adverse events (AEs) and to provide recommendations for optimizing drug therapy in pediatric patients.

Methods:

We conducted a prospective study at Stanford Hospital’s pediatric emergency department (ED) from April 2007 to April 2008 to determine the medications most frequently used in pediatric procedural sedation as well as their effectiveness and AEs. Patients, 18 years old or younger, who required procedural sedation in the pediatric ED were eligible for the study. The data collected included medical record number, sex, age, height, weight, procedure type and length, physician, and agents used. For each agent, the dose, route, time from administration to onset of sedation, duration of sedation, AEs, and sedation score were recorded. Use of supplemental oxygen and interventions during procedural sedation were also recorded.

Results:

We found that in a convenience sample of 196 children (202 procedures) receiving procedural sedation in a university-based ED, 8 different medications were used (ketamine, etomidate, fentanyl, hydromorphone, methohexital, midazolam, pentobarbital, and thiopental). Ketamine was the most frequently used medication (88%), regardless of the procedure. Only twice in the study was the medication that was initially used for procedural sedation changed completely. Fracture reduction was the most frequently performed procedure (41%), followed by laceration/suture repair (32%). There were no serious AEs reported.

Conclusion:

EM-trained physicians can safely perform pediatric procedural sedation in the ED. In the pediatric ED, the most common procedure requiring conscious sedation is fracture reduction, with ketamine as the preferred agent.     

Ketamine

There are two optical isomers of the 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone ketamine: S(+) ketamine and R(-) ketamine. Effects of this drug are mediated by N-methyl-d-aspartate (NMDA), opioid, muscarinic and different voltage-gated receptors. Clinically, the anaesthetic potency of the S(+)-isomer is approximately three to four times that of the R(-)-isomer, which is attributable to the higher affinity of the S(+)-isomer to the phencyclidine binding sites on the NMDA receptors. Ketamine is water- and lipid-soluble, allowing it to be administered conveniently via various routes and providing extensive distribution in the body. Ketamine metabolism is mediated by hepatic microsomal enzymes. It causes bronchodilation and stimulation of the sympathetic nervous system and cardiovascular system. In clinics, ketamine and particularly S(+)-ketamine are used for premedication, sedation, and induction and maintenance of general anaesthesia, which is than termed "dissociative anaesthesia". Ketamine and its S(+)-isomer are ideal anaesthetic agents for trauma victims, patients with hypovolemic and septic shock and patients with pulmonary diseases. Even subanaesthetic doses of this drug have analgesic effects, so ketamine is also recommended for post-operative analgesia and sedation. The combination of ketamine with midazolam or propofol can be extremely useful and safe for sedation and pain relief in intensive care patients, especially during sepsis and cardiovascular instability. In the treatment of chronic pain ketamine is effective as a potent analgesic or substitute together with other potent analgesics, whereby it can be added by different methods. There are some important patient side-effects, however, that limit its use, whereby psycho-mimetic side-effects are most common.     

丙泊酚合用氯胺酮在小儿腹部以下手术麻醉中的疗效观察

目的探讨丙泊酚单独使用及与氯胺酮合用在小儿椎管内麻醉中的疗效。方法选取我科40名腹部以下手术的患儿,随机分为两组(Ⅰ组和Ⅱ组),分别以单独使用丙泊酚及联合氯胺酮给药的方式,记录术中生命体征及不良事件情况。术后记录恶心、呕吐等不适及疼痛评分。结果两组术中均无呼吸暂停等严重事件发生,手术开始及手术开始后各时段Ⅰ组的生命体征均有显著差异(P<0.05),Ⅱ组手术开始时的收缩压与手术前有显著差异(P<0.05)。两组术后恢复时间与不适发生无显著差异(P>0.05),Ⅱ组术后镇痛效果优于Ⅰ组(P<0.05)。结论丙泊酚合用氯胺酮能够提供更平稳的镇静效果,减轻不良反应的发生,同时不影响苏醒时间,术后不良反应及疼痛发生率较低,是一种理想的小儿椎管内麻醉方法。     

Ketamine for conscious sedation in pediatric emergency care

The literature concerning the efficacy and safety of ketamine for conscious sedation during procedures in pediatric emergency departments was reviewed. Data were obtained from the Guidelines for Monitoring and Management of Pediatric Patients During and After Sedation for Diagnostic and Therapeutic Procedures developed by the American Academy of Pediatrics Committee on Drugs, and from a MEDLINE search (January 1966-July 2004). Search terms were conscious sedation, ketamine, and emergency department; articles relevant to pediatric age group were selected. Clinical end points were efficacy and adverse effects associated with ketamine. Ketamine was effective for conscious sedation in 89-100% of patients in various studies using intravenous, intramuscular, or oral routes of administration. The efficacy of ketamine was similar to or greater than that of other drugs, such as midazolam and the combination of meperidine, promethazine, and chlorpromazine. The main adverse effects of ketamine were emesis, recovery agitation, and emergence phenomena. Ketamine appears to be an effective and well-tolerated agent for conscious sedation in pediatric patients. Overall physician and parent satisfaction with the administration of this agent for conscious sedation was high.     

An updated review of acitretin--a systemic retinoid for the treatment of psoriasis

BACKGROUND: Acitretin is a systemic retinoid used for psoriasis. It normalizes cellular differentiation and maturation and is also used as a chemopreventive agent against cutaneous malignancies. However, it is not used frequently because of its side-effect profile. OBJECTIVE: Safety and efficacy of acitretin was evaluated as monotherapy, as well as in combination with other systemic agents. METHODS: Medical literature from 2005 to 2008 was reviewed. The most scientifically rigorous clinical trials were selected for Psoriasis Area and Severity Index. Articles were limited to case reports or clinical trials, human subjects and English language journals. RESULTS/CONCLUSION: Acitretin is effective as monotherapy for pustular and erythrodermic psoriasis and for plaque psoriasis (with other systemic agents). Side effects of acitretin use occur more commonly with high doses. Hence, acitretin is safe and effective for psoriasis.     

儿童白血病侵袭性操作镇静镇痛方案比较研究

目的:优选儿童白血病侵袭性操作镇静镇痛方案.方法:选取2011年11月至2016年11月在我院进行侵袭性操作的白血病患儿,根据选用的镇静镇痛方案分为A(咪达唑仑+局部麻醉)、B(咪达唑仑+氯胺酮+局部麻醉)、C(咪达唑仑+芬太尼+局部麻醉)、D(芬太尼+丙泊酚+局部麻醉)四组各210例.镇静效果评价参照Ramesay评...     

Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation

The ability to deliver safe and effective moderate sedation is crucial to the ability to perform invasive procedures. Sedative drugs should have a quick onset of action, provide rapid and clear-headed recovery, and be easy to administer and monitor. A number of drugs have been demonstrated to provide effective sedation for outpatient procedures but since each agent has its own limitations, a thorough knowledge of the available drugs is required to choose the appropriate drug, dose and/or combination regimen for individual patients. Midazolam, propofol, ketamine and sevoflurane are the most frequently used agents, and all have a quick onset of action and rapid recovery. The primary drawback of midazolam is the potential for accumulation of the drug, which can result in prolonged sedation and a hangover effect. The anaesthetics propofol and sevoflurane have recently been used for sedation in procedures of short duration. Although effective, these agents require monitored anaesthesia care. Ketamine is an effective agent, particularly in children, but there is concern regarding emergence reactions. AQUAVAN injection (fospropofol disodium), a phosphorylated prodrug of propofol, is an investigational agent possessing a unique and distinct pharmacokinetic and pharmacodynamic profile. Compared with propofol emulsion, AQUAVAN is associated with a slightly longer time to peak effect and a more prolonged pharmacodynamic effect. Advances in the delivery of sedation, including the development of new sedative agents, have the potential to further improve the provision of moderate sedation for a variety of invasive procedures.     

Topical amitriptyline and ketamine for post-herpetic neuralgia and other forms of neuropathic pain

Introduction: Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option.

Areas covered: This report summarizes both published and unpublished results of clinical trials with AmiKet. In post-herpetic neuralgia (PHN), AmiKet produces a significant analgesia which is comparable to that produced by oral gabapentin. In diabetic painful neuropathy, AmiKet showed a strong trend towards pain reduction. In mixed neuropathic pain, case series reports suggest a favourable response rate, but are limited by trial characteristics. AmiKet is absorbed minimally following topical administration. Over 700 patients have now received topical AmiKet in clinical regimens, and it is well-tolerated with the adverse effects mainly being application site reactions. Both agents are polymodal, and several mechanisms may contribute to the peripheral efficacy of AmiKet.

Expert opinion: Topical AmiKet has the potential to be a first-line treatment option for PHN, and to be useful in other NP conditions. Furthermore, AmiKet has the potential to be an adjunct to systemic therapies, with the targeting of a peripheral compartment in addition to central sites of action representing a rational drug combination.     

丙泊酚和瑞芬太尼对术后神清重症患者机械通气镇静和镇痛的研究

目的研究丙泊酚和瑞芬太尼镇静和镇痛对术后神清重症患者机械通气的影响。方法腹部手术患45例,随机分I组（n=15）、II组（n=15）、III组（n=15）,选择相同剂量丙泊酚和不同剂量瑞芬太尼进行镇静和镇痛,监测各组患者镇静和镇痛前后呼吸循环参数变化,Ramsay及vAS评分。结果三组呼吸循环参数给药前与给药后30min、给药后60min比较,给药后30min与给药后60min比较有统计学意义（P〈0．05）;三组镇静镇痛参数给药前与给药后30min、给药后60min比较,给药后30min与给药后60min比较有统计学意义（P〈0．05）;给药前与给药后30minVAS与Ramayl组与11组、III组P〈0＋05,给药前与给药后60minVAS与RamayI组与II组P〈0．05,I组与111组P〈0．05,VASII组与III组P〈0．05。结论对术后神清重症机械通气患者使用丙泊酚和瑞芬太尼进行镇静镇痛,在丙泊酚镇静量不变的情况下,瑞芬太尼0．1μg／（kg·min）持续静脉输注镇痛是较适宜的剂量,但可根据患者个体差异在其范围进行调整。     

Sedation and analgesia in critically ill neurologic patients

Critically ill neurologic patients can pose a challenge when it comes to providing sedation and analgesia, primarily with the balance of maintaining sedation to provide patient comfort while still allowing a neurological examination. Determination of the optimal agent requires assessment and understanding of the underlying requirement for sedation: provision of analgesia, anxiolysis, or treatment of delirium. Pharmacological options exist that can affect individual or multiple underlying sedation requirements. Numerous evaluation tools exist to monitor the efficacy of sedation as well as help clinicians titrate agents to predefined goals; these tools allow the safe administration of drugs that can otherwise have serious adverse effects. Sedation regimens must ultimately be individualized to each patient to account for differences in pharmacokinetics and dynamics of the various agents, and this is particularly true in sedating neurologically injured patients. The agents frequently used to provide sedation and analgesia in the critically ill neurologic patient will be reviewed.     

Sedation with propofol plus midazolam versus propofol alone for interventional endoscopic procedures: a prospective, randomized study

AIM: Adequate patient sedation is mandatory for most interventional endoscopic procedures. Recent anaesthesiologic studies indicates that propofol and midazolam act synergistically in combination and therefore may be superior to sedation with propofol alone in terms of sedation efficacy, recovery and costs (due to a presumed lower total dose of propofol needed). METHODS: A total of 239 consecutive patients undergoing therapeutic EGD or ERCP (EGD/ERCP-ratio, 1:1) randomly received either propofol alone (n=120, group A, loading dose 40-60 mg intravenously, followed by repeated doses of 20 mg) or propofol plus midazolam (n=119, group B, initial midazolam dose of 2. 5-3.5 mg intravenously, followed by repeated doses of 20 mg of propofol) for sedation. Vital signs (heart rate, blood pressure, oxygen saturation, electrocardiogram) were continuously monitored. Procedure-related parameters, the recovery time and quality (post-anaesthesia recovery score) as well as the patient's co-operation and tolerance to the procedure (visual analogue scale) were prospectively assessed. RESULTS: Patients of group A and B were well matched with respect to demographic and clinical data, endoscopic findings, and the type of associated procedures. In group A, a mean dose of 0.25 +/- 0.13 mg.min/kg propofol was used compared to 0.20 +/- 0.09 mg.min/kg of propofol in group B (P < 0.01, plus additional 2.9 +/- 0.5 mg of midazolam). Clinically relevant changes in vital signs were observed at comparable frequencies with a lowering of the systolic blood pressure < 90 mmHg in six out of 119 patients in group B and one out of 120 patients in group A (P=0.07). The sedation efficacy was rated similarly in both groups, whereas the mean recovery time (group A, 19 +/- 7 min vs. group B, 25 +/- 8 min, P < 0.05) as well as the recovery score (post-anaesthesia recovery score group A, 8.0 +/- 1.1 vs. post-anaesthesia recovery score group B, 7.3 +/- 1.2, P < 0.001) were significantly better with propofol alone than with propofol plus midazolam. CONCLUSION: During therapeutic endoscopy, sedation with propofol and midazolam requires a lower total dose of propofol, but otherwise has no superior sedation efficacy and is associated with a slower post-procedure recovery than sedation with propofol alone.     

咪达唑仑或丙泊酚联用右美托咪啶对颅脑创伤患者镇静作用的比较

目的:比较右美托咪啶联用丙泊酚或咪达唑仑对急性中度颅脑损伤患者镇静的临床疗效及24 h费用。方法:对75例颅脑外伤患者分别给予丙泊酚或咪达唑仑镇静,同时联合使用右美托咪啶镇静,维持镇静躁动评分(SAS)2~4分为标准,观察24 h镇静效率、生命体征、格拉斯哥昏迷程度评分(GCS)的变化,并比较两组镇静药物的总体费用。结果:右美托咪啶联用丙泊酚或咪达唑仑均能使患者达到预定的镇静镇痛目标评分,2组患者镇静前后的平均动脉压(MAP)、心率(HR)、呼吸频率(R)均有明显下降,且丙泊酚组下降幅度更明显(P<0.05);而镇静前后的血氧饱和度(SPO₂)、动脉血二氧化碳分压(PaCO₂)、GCS评分以及中心静脉压(CVP)均无明显差异(P>0.05);但联用丙泊酚组总体费用较高(558±218 比422±120,P<0.05)。结论:2组患者均可取得较好的镇静效果,但丙泊酚较咪达唑仑具有更显著的呼吸、循环抑制效应;在镇静镇痛费用方面,丙泊酚组明显高于咪达唑仑组。     

Adverse effects of sedatives in children

The application of sedation/analgesia in paediatric patients is rapidly expanding as less invasive, non-operative techniques of diagnosis and treatment are applied to the paediatric population. Medical providers who are asked to provide sedation may include radiologists, paediatricians, nurses and emergency physicians, as well as anaesthesiologists and intensive care physicians. At the same time, the range of drugs used in these settings has expanded considerably. As there is no single drug fulfilling the criteria for the ideal sedative (rapid-onset, rapid recovery, no adverse effects, immobility appropriate to procedure being performed), multiple drugs may be used in combination. It is imperative that practitioners using drugs for sedation/analgesia in children be aware of the adverse effect profile(s) of these drugs, both individually and in combination. The purpose of this review is to describe the adverse effects of sedative and reversal agents currently used in paediatric sedation/analgesia.     

Using fixed-dose combination therapies to achieve blood pressure goals

Hypertension affects an estimated 88 million Americans and is controlled to the recommended blood pressure (BP) goal of <140/90 mmHg in only 37% of individuals with hypertension. The benefits of achieving these goals, including significant reductions in cardiovascular morbidity and mortality, are well documented. Thus, a concerted effort to improve BP goal attainment is required. The majority of patients will require two or more antihypertensives to achieve BP goal. It has been shown that administering two drugs in a single-dose formulation substantially improves patient compliance compared with separate agent administration. Fixed-dose combination therapy can offer potential advantages over individual agents, including increased efficacy, reduced incidence of adverse effects, lower healthcare costs, and improved patient compliance through the use of a single medication administered once daily. Currently available fixed-dose agents include several combinations with complementary pharmacodynamic activity. This article reviews the fixed-dose antihypertensive combinations currently available in the US, and assesses the published literature comparing fixed-dose combinations with co-administration of two separate drugs or with other combinations. An analysis of the published literature between 1987 and 2007 reveals that most studies of fixed-dose antihypertensive combinations have compared the combination with monotherapy (53%); many fewer published papers have compared a fixed combination with coadministration of similar drugs as separate agents (2%), a fixed combination with another fixed combination from the same class (7%), or with a combination of agents from a different class (9%). Other comparisons have been with placebo, baseline or between generic formulations. This analysis indicates that: (i) physicians can be assured that a fixed-dose combination is more effective than either agent given as monotherapy; (ii) there is a paucity of data comparing different fixed-dose combinations; and (iii) very few studies have investigated the impact of fixed-dose combinations on achievement of BP goals, including both systolic BP and diastolic BP. For clinical decision making, physicians should rely on how the agents perform when administered together in add-on studies and how each component performs as monotherapy in reducing BP, achieving BP goals and reducing outcomes, as well as considering patient factors such as response to and tolerance of such agents as monotherapy and cost. The availability of effective and well tolerated fixed-dose combination antihypertensive agents should encourage primary-care physicians to be more willing to use such therapies in a timely manner when BP goals are not being achieved with monotherapy. This approach would improve BP control rates in the US and worldwide.     

Adverse effects of sedatives in children

The application of sedation/analgesia in paediatric patients is rapidly expanding as less invasive, non-operative techniques of diagnosis and treatment are applied to the paediatric population. Medical providers who are asked to provide sedation may include radiologists, paediatricians, nurses and emergency physicians, as well as anaesthesiologists and intensive care physicians. At the same time, the range of drugs used in these settings has expanded considerably. As there is no single drug fulfilling the criteria for the ideal sedative (rapid-onset, rapid recovery, no adverse effects, immobility appropriate to procedure being performed), multiple drugs may be used in combination. It is imperative that practitioners using drugs for sedation/analgesia in children be aware of the adverse effect profile(s) of these drugs, both individually and in combination. The purpose of this review is to describe the adverse effects of sedative and reversal agents currently used in paediatric sedation/analgesia.     

A critical review of the dosage of teicoplanin in Europe and the USA

The glycopeptide antibiotic, teicoplanin, is increasingly used in Europe in the treatment of Gram-positive infection. It is administered as a bolus once daily, it has little potential for nephrotoxicity, and serum monitoring is usually unnecessary. However, poor results were reported in early trials at a daily dose of 200 mg and, more recently, at 400 mg/day in monotherapy of staphylococcal endocarditis. While 400 mg (6 mg/kg day(-1)) is now standard, US trials have tried very high doses in an attempt to improve its efficacy in monotherapy of deep-seated staphylococcal sepsis. European centres continue to use 6 mg/kg day(-1) as the usual maintenance dose and 6-12 mg/kg as the loading dose. For the more difficult cases, teicoplanin is used in combination with other agents. All available published and unpublished literature was reviewed to try to solve these problems. With the exception of endocarditis, failure rates in the 84 European open studies varied more between trials than between the dosages used. In 32 European and eight US randomized trials, a dose of 6 mg/kg day(-1) of teicoplanin was effective, except in staphylococcal endocarditis if teicoplanin was used as monotherapy. In that case, 12 mg/kg day(-1) or more was needed to achieve a cure rate similar to that of vancomycin. Treatment was most successful with trough levels over 20 mg/l. However, lower doses were effective in combination with aminoglycosides, as is common in clinical practice. An open trial suggested that 12 mg/kg day(-1) was needed for treatment of septic arthritis. It is suggested that 6 mg/kg day(-1) of teicoplanin be used for all indications except staphylococcal endocarditis and septic arthritis when it should be given in a dose of 12 mg/kg day(-1) or in combination with other agents.