Transcutaneous carbon dioxide monitoring during prolonged apnoea with high-flow nasal oxygen.

BACKGROUND: The duration of apnoeic oxygenation with high-flow nasal oxygen is limited by hypercapnia and acidosis and monitoring of arterial carbon dioxide level is therefore essential. We have performed a study in patients undergoing prolonged apnoeic oxygenation where we monitored the progressive hypercapnia with transcutaneous carbon dioxide. In this paper, we compared the transcutaneous carbon dioxide level with arterial carbon dioxide tension. METHODS: This is a secondary publication based on data from a study exploring the limits of apnoeic oxygenation. We compared transcutaneous carbon dioxide monitoring with arterial carbon dioxide tension using Bland-Altman analyses in anaesthetised and paralysed patients undergoing prolonged apnoeic oxygenation until a predefined limit of pH 7.15 or PCO2 of 12 kPa was reached. RESULTS: We included 35 patients with a median apnoea duration of 25 min. Mean pH was 7.14 and mean arterial carbon dioxide tension was 11.2 kPa at the termination of apnoeic oxygenation. Transcutaneous carbon dioxide monitoring initially slightly underestimated the arterial tension but at carbon dioxide levels above 10 kPa it overestimated the value. Bias ranged from -0.55 to 0.81 kPa with limits of agreement between -1.25 and 2.11 kPa. CONCLUSION: Transcutaneous carbon dioxide monitoring provided a clinically acceptable substitute for arterial blood gases but as hypercapnia developed to considerable levels, we observed overestimation at high carbon dioxide tensions in patients undergoing apnoeic oxygenation with high-flow nasal oxygen.

Early postoperative recovery after peri-acetabular osteotomy: A double-blind, randomised single-centre trial of 48 vs. 8 mg dexamethasone.

BACKGROUND: Peri-acetabular osteotomy is the joint-preserving treatment of choice in young adults with hip dysplasia but is associated with intense pain and high opioid consumption postoperatively. OBJECTIVES: To investigate whether 48 mg of pre-operative dexamethasone was superior to a standard dose of 8 mg on reducing pain in the immediate postoperative phase. DESIGN: A randomised, double-blind trial. SETTING: Single-centre, primary facility. May 2017 to August 2019. PATIENTS: At least 18 years undergoing peri-acetabular osteotomy. INTERVENTIONS: Patients were randomised 1 : 1 to 48 or 8 mg dexamethasone intravenous (i.v.) as a single pre-operative injection. All patients received a standardised peri-operative protocol, including pre-operative acetaminophen and gabapentin, total i.v. anaesthesia and local anaesthetic catheter based wound administration. MAIN OUTCOME MEASURE: Number of patients with moderate/severe pain [>3 on a numeric rating scale (NRS)] in the immediate postoperative phase. RESULTS: Sixty-four patients (32 in each group) were included, and their data analysed. At some point from tracheal extubation until transfer to the ward, the NRS was more than 3 in 75% (24/32) of the 48 mg group and in 66% (21/32) in the 8 mg group, odds ratio 1.571 (95% CI, 0.552 to 4.64), P = 0.585. Patients in the 48 mg group received less opioid [cumulative rescue analgesics, oral morphine equivalents (OMEQ)] during postoperative days 0-4: median [IQR] OMEQ was 36 [15 to 85] mg vs. 79 [36 to 154] mg in the 48 and 8 mg group, respectively, P = 0.034. There were no statistically significant differences regarding complications, rate of infections or readmissions. CONCLUSION: Forty-eight milligram of dexamethasone did not reduce pain in the immediate postoperative phase compared with an 8 mg dose. We observed insignificantly lower pain scores and significantly lower cumulated opioid requirements in the 48 mg group during the first four postoperative days. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03161938, EudraCT (2017-000544-1).

Blood transfusion in the surgical treatment of adolescent idiopathic scoliosis-a single-center experience of patient blood management in 210 cases.

BACKGROUND: The surgical treatment of adolescent idiopathic scoliosis can be associated with substantial blood loss, requiring allogeneic red blood cell (RBC) transfusion. This study describes the use of RBC and the effect of a standardized perioperative patient blood management program. STUDY DESIGN AND METHODS: Patients treated with posterior instrumented fusion were consecutively enrolled over a 6-year period. Patient blood management strategies were implemented in 2011, including prophylactic tranexamic acid, intraoperative permissive hypotension, restrictive fluid therapy (including avoidance of synthetic colloids), restrictive RBC trigger according to institutional standardized protocol, the use of cell savage, and goal-directed therapy according to thrombelastography. RESULTS: In total, 210 patients were included. 64 patients (31%) received RBC transfusions. A decline in the intraoperative rate of RBC transfusion was observed, from 77% in 2011 to 13% in 2016 (p < 0.001). Patients in the transfusion group had a significantly larger major curve, lower preoperative hemoglobin, higher estimated blood loss, and an increased use of crystalloid volume resuscitation. Multiple logistic regression showed that significant predictors for RBC transfusion were preoperative hemoglobin level (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.27-0.57), estimated blood loss (OR, 1.26; 95% CI, 1.15-1.42), and year of surgery (indicating the effect of patient blood management) (OR per year, 0.76; 95% CI, 0.58-0.99). CONCLUSION: A perioperative patient blood management program substantially reduced the need for RBC transfusion. A preoperative evaluation of anemia is essential to further minimize transfusion rates.

Waking Up in Pain: a prospective unselected cohort study of pain in 3702 patients immediately after surgery in the Danish Realm.

BACKGROUND: Acute and persistent pain after surgery is well described. However, no large-scale studies on immediate postoperative pain in the operating room (OR) exist, hindering potential areas of research to improve clinical outcomes. Thus, we aimed to describe the occurrence and severity of immediate postoperative pain in a large, unselected cohort. METHODS: This was a prospective cohort study, encompassing all procedures in 31 public hospitals in the Danish Realm, during a 5-day period including the weekend. Data on procedures and anesthesia were collected and the main outcome was occurrence of moderate or severe pain in the OR. Secondary outcomes included pain, sedation and nausea in the OR or during the first 15 min in the postanesthesia care unit (PACU) including relevant risk factors. Descriptive and logistic regression statistics were used. RESULTS: A total of 3675 procedures were included for analysis (87% inclusion rate). Moderate or severe pain occurred in 7.4% (95% CI 6.5% to 8.3%) of cases in the OR immediately after awakening, rising to 20.2% in the OR and/or PACU. Large intraprocedure and interprocedure variations occurred (0.0%-37.5%), and in 20% of cases with epidural-general anesthesia patients experienced moderate or severe pain. Independent risk factors were female sex, younger age, preoperative pain, daily opioid use and major surgical procedures. CONCLUSION: Moderate or severe pain in the immediate postoperative phase occurred in 20% of all cases with procedure and anesthesiological technique variations, suggesting a need for identification of relevant procedure-specific risk factors and development of preventive treatments. TRIAL REGISTRATION NUMBER: RoPR ID 43191.

Intravenous dextromethorphan to human volunteers: relationship between pharmacokinetics and anti-hyperalgesic effect.

The aim of this study was to investigate the effect of dextromethorphan (DM) 0.5 mg/kg administered intravenously (i.v.) on hyperalgesia and pain after a tissue injury in human volunteers, and to describe the relationship between pharmacokinetic and pharmacodynamic data. The heat-capsaicin sensitisation model, a well-established experimental hyperalgesia model was induced in 24 healthy, male volunteers aged 21-35 years. The subjects received i.v. DM 0.5 mg/kg or isotonic saline on two separate study sessions. The primary outcome measure from 0 to 3 h was reduction in area of established secondary hyperalgesia. Secondary outcome measures were reduction in area of secondary hyperalgesia in response to brief thermal stimulation, heat pain detection thresholds and painfulness after tonic heat pain. Blood samples were collected throughout the study to describe the relationship between pharmacokinetic and pharmacodynamic data. Intravenous DM 0.5 mg/kg significantly reduced areas of established secondary hyperalgesia with an average of 39% (P<0.05). Development of secondary hyperalgesia was substantially prevented by DM (P<0.05). No significant effect was seen on either heat pain detection thresholds or after tonic heat pain. The pharmacokinetic-pharmacodynamic relationship showed a large inter-subject variation with a mean delay in effect of nearly 2 h in relation to peak serum concentration. The results strongly indicate that DM is an anti-hyperalgesic drug. The delay in effect may be explained by several mechanisms and suggests that timing of DM administration is an essential factor for using the drug in clinical settings.

The heat/capsaicin sensitization model: a methodologic study.

The heat/capsaicin sensitization model induces cutaneous sensitization by using a combination of heat and topical capsaicin. It has been suggested that the stability and duration of the cutaneous sensitization are due to a synergistic effect between heat and capsaicin. The aim of this study was to evaluate a possible synergistic effect between heat and capsaicin in inducing cutaneous sensitization. Twenty healthy male volunteers completed this random order, 4-session study. Three different stimulation combinations were used to induce cutaneous sensitization: day A, heat and capsaicin; day B, heat alone; day C, capsaicin alone. Combination A was repeated on day D to determine between day reproducibility. Rekindling was performed 3 times at 40-minute intervals to maintain stable areas of secondary hyperalgesia. Brief thermal sensitization (45 degrees C for 3 minutes) was induced at each session. Within and between day reproducibility was calculated. There was no difference between the size of areas of secondary hyperalgesia after stimulation with heat/capsaicin compared to heat and capsaicin stimulation alone. The within day reproducibility was better with heat/capsaicin than with either stimulation alone. There was no synergistic or additive effect between heat and capsaicin in inducing cutaneous sensitization. Rekindling seems to be the important factor in maintaining stable and long-lasting cutaneous sensitization.

Does prehospital ultrasound improve treatment of the trauma patient? A systematic review.

Ultrasound (US) has been used for in-hospital evaluation of the trauma victim for many years. The outcome in severely injured patients remains heavily influenced by initial life support and early care, as time plays a major role. Development of handheld, battery-powered, low-weight US machines has created the possibility of bringing US to the prehospital setting, thus gaining a potential for early diagnosis and treatment. The objective of this study was to systematically search the literature for evidence that prehospital US of the abdomen or thorax increases survival of trauma patients. The data regarding the use of US in the prehospital setting is sparse, often of low quality and describing a broad variety of patients and clinical challenges. Therefore, from an evidence point of view it is not possible to answer the objectives in this review. In the prehospital setting, rapid assessment plays an important role, as initial life support and early surgical care influences the outcome of the severely injured patient. Time is especially crucial in blunt abdominal trauma and penetrating truncal injuries. Several studies in this review showed that prehospital US is feasible and that the procedure is highly reliable in detection of haemoperitoneum or haemopericardium compared with the low accuracy of physical examination and haemodynamic measurements. An early diagnosis will provide the prehospital physician with the knowledge to prioritize the relevant initial treatment and to choose the closest appropriate hospital and transportation form. There is currently no evidence in the literature that prehospital US of the abdomen or thorax improves treatment of trauma patients.

Blood product ratio in acute traumatic coagulopathy--effect on mortality in a Scandinavian level 1 trauma centre.

BACKGROUND: Trauma is the leading cause of loss of life expectancy worldwide. In the most seriously injured patients, coagulopathy is often present on admission. Therefore, transfusion strategies to increase the ratio of plasma (FFP) and platelets (PLT) to red blood cells (RBC), simulating whole blood, have been introduced. Several studies report that higher ratios improve survival in massively bleeding patients. Here, the aim was to investigate the potential effect of increased FFP and PLT to RBC on mortality in trauma patients. METHODS: In a retrospective before and after study, all trauma patients primarily admitted to a level-one Trauma Centre, receiving blood transfusion, in 2001-3 (n = 97) and 2005-7 (n = 156), were included. In 2001-3, FFP and PLT were administered in accordance with the American Society of Anesthesiologists (ASA) guidelines whereas in 2005-7, Hemostatic Control Resuscitation (HCR) entailing pre-emptive use of FFP and PLT in transfusion packages during uncontrolled haemorrhage and thereafter guided by thrombelastograph (TEG) analysis was employed. The effect of transfusion therapy and coagulopathy on mortality was investigated. RESULTS: Patients included in the early and late period had comparable demography, injury severity score (ISS), admission hematology and coagulopathy (27% vs. 34% had APTT above normal). There was a significant change in blood transfusion practice with shorter time interval from admission to first transfusion (median time 3 min vs.28 min in massive bleeders, p < 0.001), transfusion of higher ratios of FFP:RBC, PLT:RBC and PLT:FFP in the HCR group but 30-day mortality remained comparable in the two periods. In the 2005-7 period, higher age, ISS and Activated Partial Thromboplastin Time (APTT) above normal were independent predictors of mortality whereas no association was fund between blood product ratios and mortality. CONCLUSION: Aggressive administration of FFP and PLT did not influence mortality in the present trauma population.

Mechanisms of postoperative pain: clinical indications for a contribution of central neuronal sensitization.

BACKGROUND: The relative importance of different nociceptive mechanisms for the intensity, duration, and character of postoperative pain is not well established. It has been suggested that sensitization of dorsal horn neurones may contribute to pain in the postoperative period. We hypothesized that wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia share a common mechanism, sensitization of central neurones, and consequently, that the short-acting opioid remifentanil would have comparable effects on hyperalgesia in both conditions. METHODS: In a randomized, controlled, double-blind trial, we assessed mechanical hyperalgesia in skin bordering the surgical wound, and an area of experimentally heat-induced secondary hyperalgesia on the thigh, in 12 patients who underwent abdominal hysterectomy within 5 days prior to the investigation. Observations were made before and during a drug challenge with remifentanil, which has been demonstrated to reduce the area of heat-induced secondary hyperalgesia in volunteers. RESULTS: The area of skin with surgically-induced mechanical hyperalgesia, the area of heat-induced secondary hyperalgesia, and pain during cough, were significantly reduced during remifentanil infusion compared with placebo (P = 0.008, P = 0.006, and P = 0.002, respectively). The relative reduction (% of baseline) of the area of skin with surgically-induced hyperalgesia and heat-induced secondary hyperalgesia during infusion of remifentanil was significantly associated (R2 = 0.72, P = 0.001). CONCLUSIONS: Although remifentanil is not a highly targeted "antihyperalgesic," these results support the hypothesis that both wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia may share common mechanisms, and that central neuronal sensitization may contribute to some aspects of postoperative pain. Antihyperalgesic drugs should be further developed and evaluated in clinical trials of postoperative pain.

Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization.

BACKGROUND: The anticonvulsant gabapentin, proven effective for neuropathic pain in two large, placebo-controlled clinical trials, is widely used for treatment of chronic pain. Preclinical studies have demonstrated analgesic and antiallodynic effects in models involving neuronal sensitization and nerve injury, without affecting acute pain transmission. The aim of the present study was to link data from animal models and clinical trials for chronic pain by investigating the effect of gabapentin on acute nociception and experimentally induced cutaneous hyperalgesia in healthy volunteers. METHODS: The human experimental hyperalgesia model, the heat-capsaicin sensitization model, was induced in 25 healthy male volunteers. Subjects received oral gabapentin (1,200 mg) or placebo after heat-capsaicin sensitization was established on the forearm. The primary outcome measures were the sizes of the areas of secondary hyperalgesia to von Frey hair and brush stimulation on the forearm. Secondary outcome measures were as follows: (1) size of secondary hyperalgesia area in response to brief thermal sensitization procedure on the thigh; (2) heat pain detection thresholds in normal and sensitized skin; and (3) painfulness of 1 min of 45 degrees C stimulation in normal skin. RESULTS: Oral gabapentin profoundly suppressed established cutaneous sensitization on the forearm and prevented development of cutaneous sensitization on the thigh. Thermal nociception in normal skin was unchanged. Side effects were modest. CONCLUSION: The results link preclinical findings with results from clinical trials of neuropathic pain. The results further suggest that gabapentin may prove effective in acute pain disorders involving neuronal sensitization, such as postoperative pain and acute herpetic pain, and could prove effective in prevention of chronic pain.

A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy.

BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 70 patients received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side effects were assessed on a four-point verbal scale 2 and 4 h postoperatively. RESULTS: Thirty-one patients in the gabapentin group and 34 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from a median of 29 (interquartile range, 21-33) to 15 (10-19) mg (P< 0.0001). Pain during movement was reduced from 41 (31-59) to 22 (10-38) mm at 2 h postoperatively (P < 0.0001) and from 31 (12-40) to 9 (3-34) mm at 4 h postoperatively (P = 0.018). No significant differences between groups were observed with regard to pain at rest or side effects. CONCLUSION: A single dose of 1,200 mg oral gabapentin resulted in a substantial reduction in postoperative morphine consumption and movement-related pain after radical mastectomy, without significant side effects. These promising results should be validated in other acute pain models involving central neuronal sensitization.