Deliberate hypotension in orthopedic surgery reduces blood loss and transfusion requirements: A meta-analysis of randomized controlled trials

PURPOSE: To determine if deliberate hypotension decreases blood loss and transfusion requirements in patients undergoing orthopedic surgery, a systematic review of all randomized trials addressing this issue was undertaken. METHODS: Electronic databases, citations lists and review articles were searched for potential articles. Relevant articles met the following inclusion criteria: English language, humans undergoing orthopedic surgery, deliberate hypotension used by any method, intraoperative blood loss measured as an outcome, and the trial methodology being randomized and controlled. Four outcomes were analyzed, including estimated blood loss, blood transfused, surgery duration, and quality of the surgical field. For all analyses, the random-effects model was used. RESULTS: Seventeen articles met the inclusion criteria. The surgeries studied included total hip arthroplasty (seven), orthognathic surgery (eight), total knee arthroplasty (one) and spinal fusion (one). A total of 636 patients were randomized across all studies. For blood loss, the overall weighted mean difference favoured treatment, with a savings of about 287 mL of blood [95% confidence interval (CI): -447, -127]. The mean differences also showed a statistically significant benefit for deliberate hypotension in reducing transfusion requirements (-667 mL of blood transfused; 95% CI: -963, -370). Deliberate hypotension was not shown to reduce the duration of surgery (-1.9 min of surgery; 95% CI: -7.2, 3.5) or improve surgical conditions (surgical field quality rating -0.5; 95% CI: -1.1, 0.2). CONCLUSION: This review provides some support for the use of deliberate hypotension in reducing blood loss and transfusion requirements in orthopedic surgery, but these results are tempered by the small sample sizes and poor methodological quality of published studies.     

Chronobiological characteristics of postoperative pain: Diurnal variation of both static and dynamic pain and effects of analgesic therapy

BACKGROUND: Previous postoperative investigations report morning peaks in analgesic administration. However, few studies have examined diurnal variation of both pain and analgesic consumption and little is known about dynamic pain in this context. METHODS: The diurnal pattern of postoperative pain is described using pain intensity and analgesic consumption data from a recently published hysterectomy trial. RESULTS: In the presence of patient-controlled analgesia with morphine, pain at 8 a.m. was significantly higher (P<0.05) than at noon, 4 p.m. or 8 p.m. on postoperative day one (for rest pain and pain evoked by sitting, forced expiration and cough) and on postoperative day two (for pain evoked by forced expiration and cough only). This temporal pattern was observed both with and without the co-administration of non-opioid analgesics (gabapentin and/or rofecoxib). Morphine use during the four hours preceding 8 a.m. on either postoperative day was not significantly lower than any of the other corresponding time intervals. CONCLUSIONS: Based on data from our post-hysterectomy analgesic clinical trial, static and dynamic pain in the morning appears to be more intense than pain later in the day. This pattern was observed in the presence of substantial nocturnal morphine use. Based on these and other previous observations, specifically designed investigations are needed to better characterize the clinical, neurohormonal and neurophysiological features of postoperative circadian pain variation - including pain during sleeping hours. If the above observations are replicated, future study of nocturnal sustained-release opioids as well as time-shifting the administration of non-opioid co-analgesic drugs to the very early morning may be warranted.     

Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the relationship to functional outcome.

Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy. INTRODUCTION: Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal involvement and disability occur. The age at which lesions are established, the pace at which the disease progresses, if (or when) the disease plateaus, and how these parameters relate to the onset of disability are unknown. To answer these questions, we performed a retrospective analysis of a group of subjects with FD. MATERIALS AND METHODS: One hundred nine subjects with a spectrum of FD were studied for up to 32 years. Disease progression was assessed in serial (99)Tc-MDP bone scans by determining the location and extent of FD lesions using a validated bone scan scoring tool. Physical function and the need for ambulatory aids were assessed. RESULTS: Ninety percent of the total body disease skeletal burden was established by age 15. Disease was established in a region-specific pattern; in the craniofacial region, 90% of the lesions were present by 3.4 yr, in the extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory aids. The median age at which assistance was needed was 7 yr (range, 1-43 yr). The median bone scan score for subjects needing assistance was 64.3 (range, 18.6-75) compared with 23.1 (range, 0.5-63.5) in the unassisted subjects (p < 0.0001). Among subjects needing assistance with ambulation, 92% showed this need by 17 yr. CONCLUSIONS: The majority of skeletal lesions and the associated functional disability occur within the first decade of life. The implication is that the window of time for preventative therapies is narrow. Likewise, therapeutic interventions must be tailored to where the patient is in the natural history of the disease (i.e., progressive disease [young] versus established disease [older subjects]). These findings have implications for prognosis, the timing and type of therapy, and the development of trials of new therapies and their interpretation.     

Predictors of non-spine fracture in elderly men: the MrOS study.

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age > or =80 years, and depressed mood. INTRODUCTION: There are few prospective studies of fracture determinants in men. We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD. MATERIALS AND METHODS: A total of 5995 men > or =65 years of age were recruited from six communities in the Unites States and followed prospectively for an average of 4.1 years. Baseline assessments of demographic, lifestyle, medical history, functional status, anthropometry, and cognitive, visual, and neuromuscular function were assessed by questionnaire or examination. Triannual mailed questionnaires ascertained incident fracture; reported fractures were adjudicated by physicians using medical records and X-ray reports. Proportional hazards models were used to develop multivariable models, selecting variables and controlling for BMD. RESULTS: Of 5876 men, 4.7% (N = 275) reported an incident nonspine fracture during follow-up (11.46/1000 person-years). Tricyclic antidepressant use (hazard ratio [HR], 2.36; 95% CI, 1.25-4.46), history of fracture at or after age 50 (HR, 2.07; 95% CI, 1.62-2.65), inability to complete a narrow walk trial (HR, 1.70; 95% CI, 1.23-2.34), falls in previous year (HR, 1.59; 95% CI, 1.23-2.05), age > or =80 years (HR, 1.33; 95% CI, 1.01-1.76), depressed mood (HR, 1.72; 95% CI, 1.00-2.95), and decreased total hip BMD (HR, 1.53; 95% CI, 1.34-1.74) were independently related to increased risk. Compared with having none (48.0% of men), having three or more of the clinical risk factors (4.9% of men) increased fracture risk 5-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile. CONCLUSIONS: Several clinical risk factors were independently associated with nonspine fractures in elderly men. The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk.     

Effect of blockade of TNF-alpha and interleukin-1 action on bone resorption in early postmenopausal women.

After acute estrogen withdrawal in postmenopausal women, administration of anakinra or etanercept, specific blockers of IL-1 and TNF-alpha, respectively, reduced the rise in bone resorption markers to about one half of that in controls. This is consistent with an important role for these immune cytokines in mediating the effect of estrogen deficiency on bone. INTRODUCTION: Studies in rodents have implicated increased production of interleukin (IL)-1 beta and TNF-alpha as mediators of bone loss after ovariectomy, but their roles are unclear in humans whose immune system differs markedly from that of rodents. MATERIALS AND METHODS: We administered transdermal estradiol, 0.1 mg/d, for 60 days to 42 early postmenopausal women. Estrogen treatment was discontinued, and subjects were randomly assigned to intervention groups receiving 3 wk of injections with 0.9% saline, anakinra 100 mg/d, or etanercept 25 mg/twice weekly. Bone turnover was assessed by measuring serum carboxyl-terminal telopeptide of type 1 collagen (CTX) and amino-terminal telopeptide of type 1 collagen (NTX), markers for bone resorption, and serum amino-terminal propeptide of type 1 collagen (P1NP), a marker for bone formation. Results were expressed as percent change in markers from baseline (last 2 days of estrogen treatment and days 20 and 21 of intervention). RESULTS: The percent changes from baseline during intervention for serum CTX, urine NTX, and serum PINP, respectively, were 43.3 +/- 8.0%, 12.0 +/- 7.1%, and -41.0 +/- 2.5% for the control group; 25.9 +/- 6.3%, 9.5 +/- 4.0%, and -37.8 +/- 3.0% for the anakinra group; and 21.7 +/- 5.0%, 0.32 +/- 3.82%, and -34.5 +/- 3.9% for the etanercept group. Compared with the control group, the blunting of the increase in serum CTX fell just below the level of significance (p=0.10) after anakinra treatment, whereas the blunting of the increase in serum CTX (p=0.034) and in urine NTX (p=0.048) were significant after etanercept treatment. Other changes were not significant. CONCLUSIONS: The data are consistent with a role for TNF-alpha, and possibly for IL-1 beta, in mediating increased bone resorption during estrogen deficiency in women. Although either cytokine blocker reduced serum CTX by about one half, the effect of combined blockade could not be tested because of concerns about toxicity. The data do not exclude direct or indirect contributory roles for RANKL or for other cytokines.     

Late-onset and Recurrent Neonatal Group B Streptococcal Disease Associated with Breast-milk Transmission

The purpose of the study was to determine the epidemiological relationships in three unrelated cases of neonatal late-onset Group B streptococcal (GBS) disease and maternal breast-milk infection with GBS. All deliveries were by cesarean section; case 1 was at term, and cases 2 and 3 were at 32- and 33-wk gestation, respectively. Case 1 relates to a mother with clinical mastitis and recurrent GBS infection in a 20-day-old male infant. Following antibiotic therapy and cessation of breast-feeding, the infant recovered without sequelae. Case 2 refers to a mother with clinical mastitis and the occurrence of late-onset GBS disease in 5-wk-old male twins. Despite intervention, one infant died and the second became ill. Following antibiotic therapy and cessation of breast-feeding, the surviving infant recovered without sequelae. Case 3 refers to a mother with sub-clinical mastitis and late-onset GBS infection occurring in a 6-day-old female twin. Following intervention, the infant recovered but suffered a bilateral thalamic infarction resulting in developmental delay and a severe seizure disorder. Following recovery of GBS from an inapparent mastitis and cessation of breast-feeding, the second infant remained well. Blood cultures from all affected infants and maternal breast milk were positive for GBS. Epidemiological relationships between neonatal- and maternal-derived GBS isolates were confirmed by a random amplified polymorphic DNA polymerase chain reaction assay (RAPD-PCR). This study is significant in that it has demonstrated that maternal milk (in cases of either clinical or sub-clinical mastitis) can be a potential source of infection resulting in either late-onset or recurrent neonatal GBS disease.     

Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment.

In a population-based cross-sectional study, we examined effects of sex and age on bone microstructure at the wrist using high-resolution 3-D pQCT. Compared with women, men had thicker trabeculae in young adulthood and had less microstructural damage with aging. These findings may contribute to the virtual immunity of men to age-related increases in wrist fractures. INTRODUCTION: Although changes in bone microstructure contribute to fracture risk independently of BMD, it has not heretofore been possible to assess this noninvasively in population-based studies. MATERIALS AND METHODS: We used high-resolution 3-D pQCT imaging (voxel size, 89 mum) to define, in a random sample of women (n = 324) and men (n = 278) 21-97 years of age, sex and age effects on bone microstructure at the wrist. RESULTS: Relative to young women (age, 20-29 years), young men had greater trabecular bone volume/tissue volume (BV/TV; by 26%, p = 0.001) and trabecular thickness (TbTh; by 28%, p < 0.001) but similar values for trabecular number (TbN) and trabecular separation (TbSp). Between ages 20 and 90 years, cross-sectional decreases in BV/TV were similar in women (-27%) and in men (-26%), but whereas women had significant decreases in TbN (-13%) and increases in TbSp (+24%), these parameters had little net change over life in men (+7% and -2% for TbN and TbSp, respectively; p < 0.001 versus women). However, TbTh decreased to a greater extent in men (-24%) than in women (-18%; p = 0.010 versus men). CONCLUSIONS: Whereas decreases with age in trabecular BV/TV are similar in men and women, the structural basis for the decrease in trabecular volume is quite different between the sexes. Thus, over life, women undergo loss of trabeculae with an increase in TbSp, whereas men begin young adult life with thicker trabeculae and primarily sustain trabecular thinning with no net change in TbN or TbSp. Because decreases in TbN have been shown to have a much greater impact on bone strength compared with decreases in TbTh, these findings may help explain the lower life-long risk of fractures in men, and specifically, their virtual immunity to age-related increases in distal forearm fractures.     

Pharmacy Fill Patterns in Young Urban Children with Persistent Asthma

Background. Medication adherence impacts healthcare utilization. Pharmacy records are useful to establish fill patterns. Objective. Use pharmacy records to establish medication patterns fill patterns for comparison to healthcare utilization. Methods. Pharmacy records of 175 children with persistent asthma were collected and compared to healthcare utilization. Results. Majority of subjects had significant healthcare utilization, low numbers of rescue medications, and poor controller medication fill rates. Those with more rescue medications had more healthcare utilization and more controller medications. Conclusions. Pharmacy fill patterns demonstrate few rescue and/or controller medication fills. Those with more rescue medications reported increased healthcare utilization despite controller medications.     

Dynamics of saccadic adaptation: differences between athletes and nonathletes.

PURPOSE: The aim of the study was to delineate differences in saccadic adaptation characteristics between a population of racquet sports athletes and nonathletes. METHODS: Eye movements were recorded at 120 Hz using a video-based eye tracker (ELMAR 2020) in a sample of 27 athletes (varsity badminton and squash players) and 14 nonathletes (<3 hours/week participation in recreational sports). Responses to negative positional error and positive positional error were studied in two sessions on separate days. Negative positional errors were induced by displacing the stimuli backwards by 3 degrees from the initial target step (12 degrees). Likewise, positive positional errors were induced by displacing the stimuli forward by 3 degrees . Amplitude gains were calculated for trials before, during, and after the adaptation phase. The magnitude and the rate of change of saccadic adaptation were determined from the amplitude gains. Differences between the groups were compared using regression analysis. RESULTS: No significant differences were found between the two groups in the magnitude of saccadic adaptation, both for negative (athletes -60%, nonathletes -57%) and positive (athletes +26%, and nonathletes +27%) positional error. Racquet sports athletes showed a significantly faster rate of adaptation for the positive positional error. A significant difference was not observed in the rate of adaptation for the negative positional error. CONCLUSIONS: Racquet sports athletes and nonathletes adapt to positional error signals by similar amounts. However, racquet sports athletes respond to positive positional errors at a faster rate, suggesting that a strategic component or environmental influences (such as practice) may play a role in saccadic adaptation.     

Assessing the Stiffness of Spinal Fusion in Animal Models

The clinical goal of spinal fusion is to reduce motion and the associated pain. Therefore, measuring motion under loading is critical. The purpose of this study was to validate four-point bending as a means to mechanically evaluate simulated fusions in dog and rabbit spines. We hypothesized that this method would be more sensitive than manual palpation and would be able to distinguish unilateral vs bilateral fusion. Spines from four mixed breed dogs and four New Zealand white rabbits were used to simulate posterolateral fusion with polymethyl methacrylate as the fusion mass. We performed manual palpation and nondestructive mechanical testing in four-point bending in four planes of motion: flexion, extension, and right and left bending. This testing protocol was used for each specimen in three fusion modes: intact, unilateral, and bilateral fusion. Under manual palpation, all intact spines were rated as not fused, and all unilateral and bilateral simulated fusions were rated as fused. In four-point bending, dog spines were significantly stiffer after unilateral fusion compared with intact in all directions. Additionally, rabbit spines were stiffer in flexion and left bending after unilateral fusion. All specimens exhibited significant differences between intact and bilateral fusion except the rabbit in extension. For unilateral vs bilateral fusion, significant differences were present for right bending in the dog model and for flexion in the rabbit. Unilateral fusion can provide enough stability to constitute a fused grade by manual palpation but may not provide structural stiffness comparable to bilateral fusion.