Patients' perspective of fast-track total joint arthroplasty: a systematic review.

The introduction of fast-track protocols decreased length of hospital stay and improved rehabilitation and outcomes in total joint arthroplasty. Despite improved clinical results published in many papers, the patient perspective of these protocols is less investigated. Purpose of this study was to explore the patient perspective of fast-track protocols in arthroplasty. A systematic search for articles of patient experiences in total hip, knee, and shoulder arthroplasty was conducted using EMBASE, MEDLINE, Cochrane, and Web-of-Science for articles published from inception to February 14, 2023. In total 12 studies were included involving 672 patients. Most patients were satisfied with short length of hospital stay and preferred rehabilitation at home with relatives for support. Various experiences were reported regarding pain and postoperative out of hospital physical therapy. Frequently, feelings of insecurity were reported because of lack of personalized information. Based on current qualitative literature, patients are satisfied with short length of hospital stay in fast-track total joint arthroplasty. Improvements in personalized information and physical therapy protocols is needed.

Perioperative systemic corticosteroids in primary unilateral total knee arthroplasty: a systematic review.

Main reasons for prolonged hospital stay after total knee arthroplasty (TKA) are postoperative nausea and vomiting (PONV) and pain. Having a positive effect on both PONV and pain, perioperative administration of corticosteroids might improve rehabilitation and reduce length of hospital stay (LOS) after TKA. Aim of this review is to determine the effect of different corticosteroid dosages on PONV, pain, and LOS in TKA. A systematic search for articles comparing dosage effects of corticosteroids regarding PONV, pain, and LOS after primary unilateral TKA was conducted using EMBASE, PubMed publisher, MEDLINE, Cochrane, Google scholar, and Web-of-Science for articles published from inception to March 17, 2022. 16 studies were included involving 2352 TKA procedures. Most studies showed reduced pain scores in corticosteroid groups and some described better pain reduction in high-dose groups. All studies showed reduced PONV in the corticosteroid groups. LOS was similar in most studies comparing placebo and perioperative corticosteroids. Only one study reported increased infection rates and intramuscular venous thrombosis in the corticosteroid group. Concluding, current literature on corticosteroids use in TKA is highly variable in type, dosage, and timing of administering medication. Overall, corticosteroids mostly reduce pain and PONV with limited effects on LOS after TKA. Only minimal statistically significant and clinically relevant benefits were found in perioperative high-dose corticosteroids compared to low-dose. Given the short follow-up in most studies, it is not possible to evaluate safety of high-dose corticosteroids.

Preoperative carbohydrate drink in fast-track primary total knee arthroplasty: a randomized controlled trial of 168 patients.

A key component in fast-track total knee arthroplasty (TKA) is early mobilization. Preoperative fasting might cause orthostatic hypotension and -intolerance which both can interfere with early mobilization. It was hypothesized that consuming a carbohydrate drink 2-3 hours prior to surgery is a viable option to reduce orthostatic hypotension, and as a result, improve rehabilitation. In this randomized controlled trial, all consecutive unilateral primary TKA patients were reviewed for eligibility. Exclusion criteria were American Society of Anesthesiologists (ASA) class above 3, older than 80 years of age, Diabetes Mellitus, and an insufficient comment of Dutch language. Patients were distributed in two groups. The control group was allowed to eat till 6 hours and drink clear fluids till 2 hours before surgery (standard treatment). The intervention group consumed, additionally to the standard treatment, a carbohydrate drink 2-3 hours before surgery. Blood pressure was measured both lying and standing as a measure for orthostatic hypotension during first time postoperative mobilization on day of surgery. A total of 168 patients were included. Prevalence of orthostatic hypotension in the control- and intervention group was 24 patients (34%) and 14 patients (19%) respectively, (p=0.05). Prevalence of orthostatic intolerance was 13 patients (19%) in the control group and 9 patients (13%) in the intervention group (p=0.32). No drink related adverse events occurred. In conclusion, taking a carbohydrate drink 2-3 hours before TKA significantly lowers the number of patients with orthostatic hypotension in early mobilization. However, the clinical relevance of the carbohydrate drink has to be studied further.

Adverse events and survival after closing- and opening-wedge high tibial osteotomy: a comparative study of 412 patients.

PURPOSE: Varus medial knee osteoarthritis (OA) can be treated with a closing-wedge (CW) or opening-wedge (OW) high tibial osteotomy (HTO). Little is known about the adverse event (AE) rate of these techniques. The purpose of this study was to examine the AE rate and survival rate of a consecutive series of 412 patients undergoing CW- or OW-HTO. METHODS: Medical records were retrospectively screened, and all patients who underwent HTO from 1993 to 2012 at the Erasmus University Medical Centre were assessed with a self-administered questionnaire. Patients filled in the intermittent and constant osteoarthritis pain score, knee injury and osteoarthritis outcome score, and a general questionnaire focusing on AE. RESULTS: Medical records of 412 patients (354 CW- and 112 OW-HTOs) were screened. Of the 358 eligible patients, 291 (81 %) returned their questionnaire. A total of 80 AE (17 %) were found in 466 osteotomies. In the CW-group, 47 (13 %) serious adverse events (SAE) and 2 (0.6 %) AE were found. In the OW-group, 17 (15 %) SAE and 14 (13 %) AE were found. The most common AE was in 14 (4 %) patients of the CW-group sensory palsy of the common peroneal nerve. The most common AE in the OW-group was persistent pain at the iliac crest [11 (9.8 %) patients]. Hardware was removed in 48 % of the CW-osteotomies and 71 % of the OW-osteotomies (p < 0.05). The probability of survival was 75 % after 10 years in the CW-group versus 90 % in the OW-group (p < 0.05). In both groups, an equal number of patients were "in need for prosthesis" according to OARSI criteria. CONCLUSION: OW-HTO was associated with more AE than CW-HTO. OW-HTO resulted in better survival than CW-HTO. However, in both groups an equal number of patients were in need for prosthesis. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Dosimetric Analyses of the Three Radiation Techniques Used in the EORTC 22922/10925 IM-MS Breast Cancer Trial.

PURPOSE: The aim of the current study is to compare the dosimetry of 3 radiation therapy (RT) techniques used in the EORTC 22922/10925 trial for irradiating the internal mammary (IM) and medial supraclavicular nodes (MS) using a treatment planning system available nowadays for dose calculation. METHODS: We performed a retrospective dosimetry analysis of anonymised data; thus, ethics approval was not required. Ten cases of left-sided breast were randomly selected for RT planning to a total dose of 50 Gy in 25 fractions. The treatment planning was done according to the trial's protocol and under the supervision of the EORTC trial's coordinators. Doses to planning target volumes (PTV) and to organs at risk (OARs) are reported. Data is presented in descriptive statistics. RESULTS: A total of 10 cases and 40 treatment plans (4 plans per case: standard-plan A, modified standard-plan B, individualised-plan C and breast-only-plan D). For all planning techniques, the mean dose to the PTV of the left breast (plan A-D) and the PTV-MS (plan A-C) exceeded 95% of the prescribed dose (>47.5 Gy). The individualised technique (plan C) had a lower coverage for PTV-IM, with a mean of 87% of the prescribed dose compared to ∼102% for plans A and B. The dose to OARs varied between techniques, with the mean heart dose being higher in the standard and modified standard techniques (18.3 and 16.6 Gy, respectively) compared to the individualised technique (9.5 Gy). CONCLUSIONS: The 3 RT techniques used in the trial varied in target coverage and OARs dose. Our results may help to understand the observed larger absolute benefit of individualised IM-MS treatment planning in terms of breast cancer outcomes.

Train-of-four ratio recovery often precedes twitch recovery when neuromuscular block is reversed by sugammadex.

BACKGROUND: Sugammadex reverses rocuronium-induced neuromuscular block (NMB). In all published studies investigating sugammadex, the primary outcome parameter was a train-of-four (TOF) ratio of 0.9. The recovery time of T1 was not described. This retrospective investigation describes the recovery of T1 vs. TOF ratio after the reversal of NMB with sugammadex. METHODS: Two studies were analyzed. In study A, a phase II dose-finding study, ASA I-II patients received an intravenous (IV) dose of rocuronium 1.2 mg/kg, followed by an IV dose of sugammadex (2.0, 4.0, 8.0, 12.0 or 16.0 mg/kg) or placebo (0.9% saline) after 5 min. In study B, a phase III trial comparing patients with renal failure and healthy controls, rocuronium 0.6 mg/kg was used to induce NMB; sugammadex 2.0 mg/kg was administered at reappearance of T2. Neuromuscular monitoring was performed by acceleromyography and TOF nerve stimulation. The primary efficacy variable was time from the administration of sugammadex to recovery of the TOF ratio to 0.9. Retrospectively, the time to recovery of T1 to 90% was calculated. RESULTS: After the reversal of rocuronium-induced NMB with an optimal dose of sugammadex [16 mg/kg (A) or 2 mg/kg (B)], the TOF ratio recovered to 0.9 significantly faster than T1 recovered to 90%. Clinical signs of residual paralysis were not observed. CONCLUSION: After the reversal of NMB by sugammadex, full recovery of the TOF ratio is possible when T1 is still depressed. The TOF ratio as the only measurement for the adequate reversal of NMB by sugammadex may not always be reliable. Further investigations for clinical implications are needed.

The relation between skin temperature increase and sensory block height in spinal anaesthesia using infrared thermography.

BACKGROUND AND OBJECTIVES: To evaluate the feasibility of determining the extent of sympathetic blockade by skin temperature measurement with infrared thermography and relate the cranial extent of the temperature increase to that of the sensory block after spinal anaesthesia. METHODS: Before and 5, 10 and 20 min after the administration of spinal anaesthesia, skin temperatures were measured with infrared thermography at the dermatomes T2-L3, in 12 male patients scheduled for lower limb surgery. The most cephalad dermatome at which sensory blockade occurred was related to the dermatome at which the largest temperature jump (corrected for baseline temperature) occurred. RESULTS: The baseline temperatures showed considerable variation across the dermatomes, being lower below T12 than at the thoracic dermatomes. The mean difference between the level of the cephalad skin temperature elevation front (mean 1.03 °C, SD 0.8 °C) and cranial sensory block height was 0.10 dermatomes (SD 1.16), correlation coefficient (0.88, P<0.001). CONCLUSION: The varying baseline temperatures across the trunk, the limited sympathetic block-induced increase in skin temperature at the trunk and the difficult control of influences from the surroundings partly obscured the extent of the skin temperature increase and its correlation to sensory block height. These factors have to be controlled to improve the use of infrared cameras as an easy bedside tool for predicting the cranial extent of (sympathetic blockade during) spinal anaesthesia.

Comparison of mechanomyography and acceleromyography for the assessment of rocuronium induced neuromuscular block in myotonic dystrophy type 1.

We measured acceleromyography and mechanomyography simultaneously with monitoring of rocuronium-induced neuromuscular block in four patients with myotonic dystrophy type 1. Furthermore, we compared neuromuscular block measures from these patients with those from normal controls from previous studies. In myotonic dystrophy type 1 patients, the dose-response curve obtained with acceleromyography was steeper and right-shifted compared with that obtained using mechanomyography. However, the effective doses to produce 95% neuromuscular block determined with both acceleromyography and mechanomyography were similar to each other and to values found in normal patients. In the three myotonic dystrophy type 1 patients with mild to moderate disease, times to recovery from block were similar to those observed in normal controls. In both patients and normal controls, neuromuscular block recovered faster with acceleromyography. However, in one patient with severe muscle wasting, recovery of neuromuscular block was prolonged. We conclude that mechanomyography and acceleromyography cannot be used interchangeably to monitor neuromuscular block in myotonic dystrophy type 1 patients.

A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex.

A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs predispose such patients to severe postoperative residual paralysis and respiratory complications. Sugammadex binds steroidal NMBDs and, therefore reverses a rocuronium or vecuronium-induced NMB, without interfering with cholinergic transmission. A rapid and complete recovery from profound NMB was achieved and no adverse events were observed. This case suggests that sugammadex is a safe and effective antagonist of a rocuronium induced NMB blockade in patients with myasthenia gravis.

Continuous femoral nerve block after total knee arthroplasty?

BACKGROUND: A continuous femoral nerve block is frequently used as an adjunct therapy after total knee arthroplasty (TKA). However, there is still debate on its benefits. METHODS: In this prospective, randomized study, patients received a basic analgesic regimen of paracetamol and dicloflenac for the first 48 h postoperatively. In addition, the study group received a continuous femoral nerve block. A morphine patient-controlled analgesia pump was also available as a rescue analgesic to all the patients. Patients' numeric rating scores for pain, the amount of morphine consumed and its side effects during the first 48 h were recorded. Knee flexion angles achieved during the first week were registered. Three months postoperatively, patients completed Western Ontario and McMaster Universities Osteoarthritis Index and Knee Society Score. RESULTS: The study group (n=27) had less pain (P=0.0016) during the first 48 h, was more satisfied with the analgesia (P<0.001) and used less morphine (P=0.007) compared with the control group (n=26). Fewer patients were nauseated, vomited or were drowsy in the study group (P=0.001). Also, the study group achieved better knee flexion in the first 6 days after surgery (P=0.001), with more patients reaching 90 degrees flexion than the control group. However, after 3 months, there were no significant functional differences between the groups. CONCLUSION: A continuous femoral nerve block leads to better analgesia, less morphine consumption and less morphine-related side effects after TKA. Early functional recovery is improved, resulting in more patients reaching 90 degrees knee flexion after 6 days. However, after 3 months, no significant functional benefits were found.

Isoflurane attenuates pulmonary interleukin-1beta and systemic tumor necrosis factor-alpha following mechanical ventilation in healthy mice.

BACKGROUND: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro-inflammatory state is a risk factor for ventilator-induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV-induced inflammatory response in healthy lungs is reduced by isoflurane. METHODS: Healthy C57BL6 mice (n=34) were mechanically ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cmH(2)O; and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC isoflurane. Cytokine levels were measured in lung homogenate and plasma. Leukocytes were counted in lung tissue. RESULTS: Lung homogenates: MV increased pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no significant increase in interleukin (IL)-1beta was found compared with non-ventilated control mice. PLASMA: MV induced a systemic pro-inflammatory response. In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no significant increase in tumor necrosis factor (TNF)-alpha was found compared with non-ventilated control mice. CONCLUSIONS: The present study is the first to show that isoflurane attenuates the pulmonary IL-1beta and systemic TNF-alpha response following MV in healthy mice.

In vivo animal studies with sugammadex.

A review is presented of animal studies of the selective steroidal neuromuscular blocking drug binding agent sugammadex. These studies demonstrate that sugammadex is faster in onset than the currently used acetylcholinesterase inhibitors, has no muscarinic effects, and is characterised by lack of adverse effects on other organs. These results offer support for the further development of sugammadex for clinical use in humans.

A needle guidance device compared to free hand technique in an ultrasound-guided interventional task using a phantom.

In this in vitro study, a needle guidance device and a 'free hand' technique for ultrasound guided needle insertion were compared in a simulated ultrasound-guided interventional task using a porcine phantom. Residents inexperienced in using ultrasonography were asked to insert a needle, using an in-plane techniques, and to make contact with metal rods at a depth of 2 and 4 cm in the phantom. The transducer made angles of 90 degrees, 60 degrees and 45 degrees with the surface of the phantom. The times to perform the procedures were significantly shorter and the needle visualisation was significantly better when using the needle guidance device. The residents ranked their satisfaction with the needle-guidance device significantly better than the 'free-hand' technique. This device may be beneficial when performing ultrasound guided peripheral nerve blocks, especially by inexperienced operators.

Two years' experience with inspiration breath-hold in liver SBRT.

•The workflow of inspiration breath-hold SBRT for liver metastases is described.•Inspiration breath-hold in liver SBRT is feasible for 95% of the patients.•An individual margin recipe for inspiration breath-hold liver SBRT is explained.•Margin reduction of 10 mm using inspiration breath-hold compared to free breathing.

Depth of the thoracic epidural space in children.

Thoracic epidural anaesthesia in anaesthetized children requires a meticulous technique and may have an increased success rate when the distance between skin and epidural space is known. The objective of this observational study was to measure the skin to epidural distance (SED) during thoracic epidural puncture in 61 children. The epidural puncture was performed using the loss of resistance technique with saline 0.9%. The distance from the needle tip to the point where the needle emerged from the skin was measured. The post-operative analgesia parameters were also measured. Skin to epidural distance correlated significantly with the age and weight of the children. The equation for the relation between SED (cm) and age was 2.15 + (0.01 x months) and for SED vs weight was 1.95 + (0.045 x kg). Despite considerable variability among individuals, the observed correlation of SED with both age and weight shows that this parameter may be helpful to guide thoracic epidural puncture in anaesthetized children.

Presence of anti-La(SS-B) is associated with binding to the 13-kD carboxyl terminus of 60-kD Ro(SS-A) in systemic lupus erythematosus.

In systemic lupus erythematosus (SLE) clinical manifestations, autoantibody production, and immunogenetics are inter-related. The ability to study parts of the autoimmune response may allow a more detailed understanding of these relationships. We undertook this study to determine whether the fine specificity of the autoimmune response to 60-kD Ro(SS-A) was related to the presence of other autoantibodies. We screened 74 patients with SLE for antibodies to the carboxyl 13-kD terminal of 60-kD Ro(SS-A) (13 kD). Twenty-five sera had such antibodies. This reactivity was distinguished by the presence of not only anti-Ro(SS-A) but also other antibodies. All nine sera with Ro(SS-A) and La(SS-B) Ouchterlony immunodiffusion precipitins bound 13-kD (p = 0.01), whereas 10 of 11 sera with both anti-Ro(SS-A) and anti-La(SS-B) as determined by immunosorbent assay bound 13-kD (p = 0.002). Inhibition studies demonstrated that antibodies binding the 13-kD fragment bound the 60-kD Ro(SS-A) protein but did not bind the La(SS-B) protein. Thus, anti-La(SS-B) was found in those sera that bound epitopes within the 13-kD carboxyl terminal of 60-kD Ro(SS-A). These data suggest a structural basis by which anti-Ro(SS-A) and anti-La(SS-B) are coupled in SLE.

Non-depolarizing neuromuscular blocking activity of bisquaternary amino di- and tripeptide derivatives.

Herein we describe the synthesis of novel di- and tripeptide derivatives with two quaternary nitrogen groups attached and the biological testing of these compounds for neuromuscular blocking (NMB) activity in vitro and in vivo. The short peptide scaffold was selected because it offers potential for desired distance between the two pharmacophoric quaternary nitrogen groups, short duration of action, straightforward synthesis, and compatibility with an injectable formulation. From a small series of compounds 20c,e are identified as effective non-depolarizing NMB agents in vitro and in vivo in anesthetized cats and Rhesus monkeys with potencies similar to those of the clinical reference compounds rocuronium (4) and suxamethonium (2) (monkey ED(90) = 0.68, 0.23, 0.16, 5.04 micromol/kg, respectively). These new peptide derivatives 20c,e have similar potency and onset time but longer duration and slower recovery than the clinically used reference compounds. The structure-activity relationships described for this chemical series lead to the conclusion that the di- or tripeptide fragment can be regarded as an alternative template to the steroid or aliphatic ester of previously reported NMBs and within this tripeptide-derived series clog P correlates well with in vitro NMB activity.

Variations of the phosphorylation of 1-beta-D-arabinofuranosylcytosine (ARA-C) in human myeloid leukemic cells related to the cell cycle.

Bone marrow cells of five patients with acute myeloid leukemia were fractionated by means of counterflow centrifugation (elutriation). The different fractions were enriched with cells belonging to subsequent stages of the cell cycle. Cytokinetic evaluation of these cell fractions was performed by [3H]thymidine autoradiography, [3H]thymidine incorporation and DNA/RNA-flow cytometry. Phosphorylation of cytosine arabinoside (ara-C, 1-beta-D-arabinofuranosylcytosine) in the different fractions was measured by incubation of the cells for 30 min with 1.07 microM [3H]ara-C. Phosphorylation of ara-C in the whole bone marrow samples ranged from 5.9 to 33.2 pmol/10(6) cells. In the fractions containing only G1-phase cells, phosphorylation ranged from 1.2 to 19.5 pmol/10(6) cells. The phosphorylation seems to increase before DNA synthesis starts. Maximal activities were found in the fractions enriched with cells in late G1- or S-phase of the cell cycle. In these fractions the ara-C phosphorylating activity was 1.5-8 times higher compared to the fractions with the lowest activity. One may therefore assume that not only S-phase cells are killed by ara-C, but that G1-phase cells which can phosphorylate ara-C, may also be doomed when they enter S-phase, since the elimination of the intracellular cytosine arabinoside tri-phosphate (ara-CTP) is a relatively slow process. The fraction of G1-phase cells phosphorylating ara-C, may be an important determinant in the extent of the cell-killing effect of ara-C treatment in the different leukemias.