Hannu Kokki

Pain after cardiac surgery: a prospective cohort study of 1-year incidence and intensity.

Background: Persistent chest pain may originate from cardiac surgery. Conflicting results have been reported on the incidence of persistent poststernotomy pain with considerable discrepancies between the retrospective reports and the one prospective study conducted to assess this pain. Therefore, the authors conducted a follow-up survey for the first 12 months after cardiac surgery in 213 patients who had a sternotomy. Methods: The authors performed a prospective inquiry of acute and chronic poststernotomy pain both before and after cardiac surgery. Two hundred thirteen coronary artery bypass patients received a questionnaire preoperatively, 4 days postoperatively, and 1, 3, 6, and 12 months postoperatively. All patients were asked about their expectations, their preferences, and the location and intensity of postoperative pain. Results: The return rates for the postal questionnaires were 203 (95%) and 186 (87%) after 1 and 12 months, respectively. Patients experienced more pain postoperatively at rest than they had expected to preoperatively. At rest, the worst actual postoperative pain was 6 (0–10), and the worst expected pain as assessed preoperatively was 5 (0–10) (P = 0.013). The worst reported postoperative pain was severe (numeric rating scale score 7–10) in 49% at rest, in 78% during coughing, and in 62% of patients on movement. One year after the operation, 26 patients (14%) reported mild chronic poststernotomy pain at rest, 1 patient (1%) had moderate pain, and 3 patients (2%) had severe pain. Upon movement, persistent pain was even more common: 45 patients (24%) had mild, 5 patients (3%) had moderate, and 7 patients (4%) had severe pain. Patients who experienced moderate to severe acute postoperative pain also reported any chronic poststernotomy pain (numeric rating scale score 1–10) more frequently. Conclusions: Although common, the incidence of persistent pain after sternotomy was lower than previously reported. Also, reassuringly, 1 year after surgery this pain was mostly mild in nature both at rest and on movement.

Off-label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature.

Objectives:  In paediatric pharmacotherapy, many drugs are prescribed to be given in ways and for conditions not approved in the marketing authorization (MA). Thus, off‐label prescribing of drugs with no MA is widespread in paediatric wards. However, drug MA status and clinical practices differ across countries. In this prospective study, we studied the prescribing of off‐label and unlicensed drugs in three paediatric wards in a tertiary hospital in Finland. Furthermore, we reviewed previous published studies to provide an up‐to‐date international perspective on prescribing of off‐label and unlicensed drugs for hospitalized children.

Serotonin and dopamine transporter binding in children with autism determined by SPECT

Disturbances in the serotonergic system have been recognized in autism. To investigate the association between serotonin and dopamine transporters and autism, we studied 15 children (14 males, one female; mean age 8y 8mo [SD 3y 10mo]) with autism and 10 non‐autistic comparison children (five males, five females; mean age 9y 10mo [SD 2y 8mo]) using single‐photon emission computed tomography (SPECT) with [123I] nor‐β‐CIT. The children, with autism were studied during light sedation. They showed reduced serotonin transporter (SERT) binding capacity in the medial frontal cortex, midbrain, and temporal lobe areas. However, after correction due to the estimated effect of sedation, the difference remained significant only in the medial frontal cortex area (p=0.002). In the individuals with autism dopamine transporter (DAT) binding did not differ from that of the comparison group. The results indicate that SERT binding capacity is disturbed in autism. The reduction is more evident in adolescence than in earlier childhood. The low SERT binding reported here and the low serotonin synthesis capacity shown elsewhere may indicate maturation of a lesser number of serotonergic nerve terminals in individuals with autism.

Paracetamol (acetaminophen) penetrates readily into the cerebrospinal fluid of children after intravenous administration

INTRODUCTION. The main action of paracetamol (acetaminophen) is presumed to be in the central nervous system. The central nervous system penetration of paracetamol has been described in children with intracranial pathologies but not in children with an intact blood-brain barrier. OBJECTIVE. We investigated the cerebrospinal fluid penetration of paracetamol in 32 healthy children, aged 3 months to 12 years, who were undergoing surgery in the lower body using spinal anesthesia. MATERIALS AND METHODS. In this open-label prospective study, children were given a single intravenous injection of paracetamol (15 mg/kg). Cerebrospinal fluid and venous blood samples were obtained between 5 minutes and 5 hours after injection. Paracetamol concentrations were determined from the cerebrospinal fluid and plasma by using a fluorescence polarization immunoassay. RESULTS. Paracetamol was detected in cerebrospinal fluid from the earliest sample at 5 minutes, although in this sample paracetamol concentration was below the limit of quantification of 1.0 mg/L. Subsequent paracetamol concentrations in cerebrospinal fluid ranged between 1.3 and 18 mg/L (median: 7.2 mg/L), plasma concentrations ranged between 2.4 and 33 mg/L, and cerebrospinal fluid/plasma ratios ranged between 0.06 and 2.0. The highest CSF paracetamol concentration was detected at 57 minutes. CONCLUSIONS. Paracetamol permeates readily into the cerebrospinal fluid of children. This fast and extensive transfer enables the rapid central analgesic and antipyretic action of intravenous paracetamol.

S(+)-ketamine as an analgesic adjunct reduces opioid consumption after cardiac surgery

There are no studies evaluating S(+)-ketamine for pain management after sternotomy. In this prospective, randomized, double-blind, placebo-controlled clinical trial, we evaluated the efficacy and feasibility of S(+)-ketamine as an adjunctive analgesic after cardiac surgery. Ninety patients scheduled for elective coronary artery bypass grafting (CABG) were randomized to receive either a 75 μg/kg bolus of S(+)-ketamine followed by a continuous infusion of 1.25 μg · kg−1 · min−1 for 48 h (n = 44) or placebo (normal saline bolus and infusion) (n = 46). From the time of tracheal extubation, patients could access an opioid (oxycodone) via a patient-controlled analgesia device, and the cumulative oxycodone doses were measured over 48 h. Pain was evaluated on a visual analog scale three times daily. The quality of recovery, patient satisfaction with pain management, and adverse effects were recorded. The cumulative oxycodone consumption during the first 48 postoperative hours was less in the S(+)-ketamine group (103 ± 44 mg) than in the placebo group (125 ± 45 mg; mean difference, 22 mg; 95% confidence interval for the difference, 3–40 mg; P = 0.023). Pain scores did not differ between the groups at rest (P = 0.17) or during a deep breath (P = 0.23). Patient satisfaction was superior in S(+)-ketamine-treated patients: 26 (60%) of 44 in the S(+)-ketamine group compared with 16 (35%) of 46 in the placebo group were very satisfied with the analgesic management (P = 0.032). Nausea and vomiting were the most common adverse events, with similar frequencies in both groups. Four patients in the S(+)-ketamine group developed transient hallucinations during the infusion, versus none in the placebo group. In conclusion, small-dose S(+)-ketamine decreased opioid consumption in CABG patients during the first 48 h after surgery.

Comparison of pre‐ and postoperative administration of ketoprofen for analgesia after tonsillectomy in children

Background: Tonsillectomy is commonly performed in children, but unfortunately it is associated with intense postoperative pain. The use and optimal timing of nonsteroidal anti‐inflammatory drugs (e.g. ketoprofen) during tonsillectomy is controversial.

Postdural puncture headache is not an age‐related symptom in children: a prospective, open‐randomized, parallel group study comparing a22‐gauge Quincke with a 22‐gauge Whitacre needle

Many reports have shown a low incidence of postdural puncture headache (PDPH) and other complaints in young children. The objective of this open‐randomized, prospective, parallel group study was to compare the use of a cutting point spinal needle (22‐G Quincke) with a pencil point spinal needle (22‐G Whitacre) in children. We studied the puncture characteristics, success rate and incidence of postpuncture complaints in 57 children, aged 8 months to 15 years, following 98 lumbar punctures (LP). The patient/parents completed a diary at 3 and 7 days after LP. The response rate was 97%.

Celecoxib and ketoprofen for pain management during tonsillectomy: a placebo-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of celecoxib and ketoprofen in pain management during tonsillectomy in 120 patients. STUDY DESIGN AND SETTING: The study was randomized, double-blind, and placebo-controlled with parallel groups. Sixty minutes before anesthesia induction and 12 hours after, the patients received a 200-mg celecoxib, a 100-mg ketoprofen, or a placebo capsule. After discharge, patients were prescribed either celecoxib or ketoprofen capsules to be taken every 12 hours. RESULTS: During the first 24 hours, the need for rescue analgesic was less in the ketoprofen-group (5 (1-9)) doses (median (range)) than in the placebogroup (6 (1-13)) (P = 0.021), but similar to the cele-coxib-group (5 (2-14)). After discharge, the cessation of pain during eating occurred earlier in the celecoxib-treated patients, after 10 (1-17) days, than in the ketoprofen-treated patients, after 12 (1-21) days, (P = 0.008). One celecoxib-treated patient and 6 ketoprofen-treated patients (P = 0.013) needed electrocautery to stop postoperative bleeding. CONCLUSION: Ketoprofen provided a better initial analgesic efficacy but after discharge the recovery with celecoxib was faster and the incidence of secondary hemorrhages was lower. SIGNIFICANCE: Celecoxib seems to be more effective and safe than ketoprofen for pain management after discharge in patients with tonsillectomy.

Pharmacokinetics of Oxycodone After Intravenous, Buccal, Intramuscular and Gastric Administration in Children

ObjectiveTo evaluate the pharmacokinetics of four administration routes of oxycodone parenteral liquid (10 mg/mL), single intravenous and intramuscular injections and buccal and gastric administration, in children.Patients and participantsForty generally healthy children, aged 6–93 months, undergoing inpatient surgery.MethodsAfter induction of anaesthesia, children received a single dose of oxycodone 0.1 mg/kg intravenously (n = 9), intramuscularly (n = 10), buccally (n = 11) or via an orogastric tube into the stomach (n = 10). Regular blood samples were collected up to 12 hours, and plasma was analysed for oxycodone using gas chromatography-mass spectrometry (limit of quantification 1 µg/L).ResultsThe peak drug concentration observed was 57–110 (mean 82) µg/L after intravenous administration, 23–54 (34) µg/L after intramuscular administration, 3.9–14 (9.8) µg/L after buccal administration and 1.7–15 (9.2) µg/L after gastric administration. The time to peak concentration was 2–30 (16) minutes in the intramuscular group, 30–480 (221) minutes in the buccal group and 60–360 (193) minutes in the gastric group. The terminal elimination half-lives were closely similar in the four groups: 124–208 (163) minutes in the intravenous group, 162–227 (150) minutes in the intramuscular group, 73–234 (150) minutes in the buccal group and 80–246 (147) minutes in the gastric group. Area under the concentration-time curve (AUC) was 5037–8954 (6612) µg · min/L in the intravenous group, 3084–5524 (4473) µg · min/L in the intramuscular group, 1444-5560 (3658) µg · min/L in the buccal group and 692–3843 (2436) µg · min/L in the gastric group. The estimated bioavailability (AUC/mean intravenous AUC) of intramuscular oxycodone was 0.47–0.84 (0.68), that of buccal oxycodone 0.22–0.84 (0.55) and that of gastric oxycodone 0.10–0.58 (0.37).ConclusionThe pharmacokinetics of intravenous oxycodone in children aged 6–93 months are fairly similar to those reported in adults. Intramuscular administration provides relatively constant drug absorption, but after buccal and gastric administration the interindividual variation in the rate and extent of absorption is large.

Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism

There has been little exploration of major biologic regulators of cerebral development in autism. We measured insulin-like growth factors (IGF) -1 and -2 from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism (median age 5y 5mo; range 1y 11mo-15y 10mo; 20 males, 5 females), and in 16 age-matched comparison children without disability (median age 7y 4mo; range 1y 1mo-15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further correlated with age of patients and head size. CSF IGF-1 concentration was significantly lower in patients with autism than in the comparison group. The CSF concentrations of children with autism under 5 years of age were significantly lower than their age-matched comparisons. The head circumferences correlated with CSF IGF-1 in children with autism but no such correlation was found in the comparison group. There was no difference between the two groups in CSF IGF-2 concentrations. No patients with autism had macrocephaly. We conclude that low concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis in autism because IGF-1 is important for the survival of Purkinje cells of the cerebellum. The head growth might be explained by the actions of IGF-1 and -2 reflected in CSF concentrations.