Pain relief during labour and following obstetric and gynaecological surgery with special reference to neuroaxial morphine

Background: Pain is a major clinical problem during childbirth and postoperatively after caesarean section (CS) and hysterectomy. There are several reasons why pain should be minimized; pain is indeed a negative sensation, it affects the birth-experience and the entire post-operative recovery, with reduced wellbeing and extended time in hospital. Inadequately treated pain is a risk factor for persistent pain. Multimodal pain treatment, combining different analgesics with different mode of action to reach additive or synergistic analgesic effect; thereby gain effective pain management but a lower incident of side effects has become praxis. Adding small amounts of morphine to local anaesthetic for spinal anaesthesia is an attractive combination improving intraoperative anaesthesia and postoperative analgesia. The use of intrathecal morphine (ITM) is however associated to side effects, where respiratory depression is the most feared adverse effect, which restricted its use. Obesity per se is associated with risk for respiratory complications e.g. sleep apnoea and hypoventilation. Thus obesity, ITM and pregnancy may act additive increasing risk for respiratory depression and the risk for respiratory depression has been seen more commonly in obese mothers after caesarean section CS. The aim of this thesis was to study morphine as adjunct to bupivacaine in neuroaxial anaesthesia in different perspectives; ITM used in spinal labour analgesia, ITM used in spinal for post hysterectomy pain, the use of neuroaxial administered morphine in Sweden, the role of polygraphic registration in obese mothers after CS in spinal anaesthesia including ITM and finally the use of general and regional anaesthesia ITM in emergent CS. Methods and Main Results: Study I and II are randomized double-blinded placebocontrolled trials investigating the effects of different doses of morphine added to local anaesthetic intrathecally. In Study I we compared the addition of morphine 50, 100 µg or saline to intrathecal bupivacaine (1.25 mg) and sufentanil (5 µg) to evaluate the impact on duration of labour analgesia as part of a combined spinal-epidural technique in 90 nulliparous labouring women. Duration of analgesia was defined as the time from intrathecal injection to the return of pain VAS >4. No significant differences were seen in onset or duration of analgesia, obstetric and neonatal outcome or side effects, between the groups. In Study II ASA I-II women (n=144) scheduled for abdominal hysterectomy in combined general and spinal anaesthesia were randomised to spinal anaesthesia with 12 mg of hyperbaric bupivacaine combined with 100, 200, and 300 µg morphine or saline. Primary outcome was 24 h used nurse administered and patient controlled analgesia (PCA)-morphine. ITM reduced accumulated 24 h post-operative morphine consumption. Morphine 100 µg reduced morphine consumption significantly vs. placebo at 0–6 h, 6–12 h, and for the entire 0–24 h after operation. Morphine 200 µg further reduced morphine consumption significantly vs. morphine 100 µg at 0–6 h and for the entire 0–24 h after operation. Morphine 300 µg did not further reduce the morphine consumption. Emesis was experienced similar in all groups, and pruritus occurred only in the morphine groups. No serious side effects were observed. In Study III we investigated the use of intrathecal and epidural opioids in mainly CS, and hysterectomies in Sweden by a questionnaire to anaesthetists in charge of obstetric anaesthesia units. We had 68% of units responding and found in CS spinal anaesthesia, 20/32 units use ITM, the most common dose was 100 µg (17/21). Addition of intrathecal fentanyl (10-20 µg) or sufentanil (2.5-10 µg), was used by 21 and 9 units respectively. In CS epidural anaesthesia 12/32 clinics used epidural morphine, the majority of units used a 2 mg dose while use of fentanyl (50-100 µg) or sufentanil (5-25 µg) was more common, in 10 and 15 units respectively. For hysterectomy ITM was used by 20/32 units (80-200 µg), the majority used 200 µg dose (9/32). Risk of respiratory depression and difficult to monitor postoperatively was the main reason for withholding intrathecal opioids in 7/12 units. Study IV is a prospective observational study to explore the occurrence of sleep disorder breathing in obese mothers and use of portable sleep apnoea polygraphy for respiratory monitoring the first night after CS with bupivacaine/morphine/fentanyl spinal anaesthesia, assessing the occurrence of apnoea/hypopnea index (AHI) and oxygen desaturation index (ODI). Among the 20 mothers that completed polygraphic registration: 11 had normal apnoea-hypopnea index (AHI <5) 7 had mild; AHI ≥5 and <15; and 2 had moderate; AHI ≥15 (15.3 and 18.2) but no one had severe obstructive sleep apnoea, OSA (AHI ≥30). Those mothers with moderate OSA did not show high ODI or signs of hypercapnia on transcutaneous CO2 registration. The ODI was on average 4.4, eight mothers had an ODI >5. Mean saturation was 94% (91-96%), and four mothers had mean saturation between 90-94%, but none had a mean SpO2 <90%. None of the mothers showed clinical signs or symptoms of severe respiratory depression, registered by routine clinical monitoring. Study V is a retrospective chart review of emergency CS (ECS) at Danderyd Hospital between January and October 2016 with the aim to assess the decision to delivery interval (DDI) and the impact of chosen anaesthetic technique, general anaesthesia (GA), spinal anaesthesia (SA) with opioid supplementation, or “top-up” of labour epidural analgesia (tEDA) with local anaesthesia and fentanyl mixture, and work shift for ECS at Danderyd Hospital, Sweden. In total, 135 ECS were analysed: 92% were delivered within 30 minutes. Mean DDI for all CS was 17.3 ± 8.1 minutes. With GA DDI was shortened by 10 and 13 minutes compared to SA and tEDA (p<0.0005). DDI for SA and tEDA was similar. No difference in DDI was seen regarding time of day or weekday. Apgar <7 at 5 min. was found more commonly in ECS having GA (11/64) vs. SA (2/30) and tEDA (1/41)(p<0.05). Conclusions: Low dose ITM has an important role mainly in a fast track concept to minimize systemic opioid consumption and still optimize postoperative analgesia in elective and emergent CS in recommended dose of 100 µg and hysterectomy 200 µg. If spinal labour analgesia is chosen addition of ITM doses 100 µg or less seems of no value to prolong the duration. ITM is widely used in Sweden in mainly CS and hysterectomy, although still restricted in some units due to fear of respiratory depression and/or difficulties monitoring postoperatively. Respiratory monitoring with polygraphy in obese mothers after CS ITM anaesthesia did not reveal severe sleep disorder breathing and seems to be of limited value in the postoperative period after CS performed in spinal anaesthesia including morphine. We found 92% of ECS, were delivered within 30 min. and DDI was shortened with GA by 10 and 13 minutes compared to SA and tEDA but with no difference between SA and tED

Circulatory collapse following epidural bolus for Caesarean section a profound vasovagal reaction? A case report

AbstractIntroductionReduced blood pressure is commonly seen associated to spinal anaesthesia for Caesarean section and efforts to reduce its occurrence and its magnitude is common practice. Cardiovascular collapse requiring cardio-pulmonary resuscitation after putting the spinal/epidural block for Caesarean section is however a rare but most dramatic event.Presentation of caseWe describe a case with sudden short loss of circulation, circulatory collapse, short after start of emergency Caesarean section in top up epidural anaesthesia (3+12ml ropivaciane 7.5mg/ml), requiring CPR. The neonate was delivered during CPR with Apgar 1, 10, 10 at 1, 5 and 10min. Circulation was restored following 60–90s of CPR and administration of 0.5mg adrenaline. No cardioversion was administered sinus rhythm was regained spontaneously. The mother and child had a further uncomplicated course. No signs of cardiac damage/anomaly, emboli, septicaemia, pereclampisa or local anaesthetic toxicity was found. The patient had prior to the decision about Caesarean section had fever and was subsequently relatively dehydrated.DiscussionThe patient had a fast return of sinus rhythm following birth of the child, without cardioversion. None of common causes for cardiac arrest was found and the patient an uncomplicated post Caesarean section course. The combination of epidural induced sympathetic block and reduced preload possibly triggered a Bezold-Jarisch reflex with a profound vasovagal reaction.ConcluiosnA structured plan for the handling of cardiovascular crisis must be available wherever Caesarean section are performed. Adequate volume loading, left tilt and vigilant control of circulation following regional block performance is of outmost importance

Sevoflurane requirement during elective ankle day surgery: the effects of etirocoxib premedication, a prospective randomised study

<p>Abstract</p> <p>Background</p> <p>Anti-inflammatory drugs, NSAIDs, have become an important part of the pain management in day surgery. The aim of the present study was to evaluate the effect of Coxib premedication on the intra-operative anaesthetic requirements in patients undergoing elective ankle surgery in general anaesthesia.</p> <p>Type of study</p> <p>Prospective, randomized study of the intra-operative anaesthetic-sparing effects of etoricoxib premedication as compared to no NSAID preoperatively.</p> <p>Methods</p> <p>The intra-operative requirement of sevoflurane was studied in forty-four ASA 1–2 patients undergoing elective ankle day surgical in balanced general anaesthesia.</p> <p>Primary study endpoint was end-tidal sevoflurane concentration to maintain Cerebral State Index of 40 – 50 during surgery.</p> <p>Results</p> <p>All anaesthesia and surgery was uneventful, no complications or adverse events were noticed. The mean end-tidal sevoflurane concentration intra-operatively was 1.25 (SD 0.2) and 0.91 (SD 0.2) for the pre and post-operative administered group of patients respectively (p < 0.0001). No other intra-operative differences could be noted. Emergence and recovery was rapid and no difference was noticed in time to discharge-eligible mean 52 minutes in both groups studied. In all 6 patients, 5 in the group receiving etoricoxib post-operatively, after surgery, and one in the pre-operative group required rescue analgesia before discharge from hospital. No difference was seen in pain or need for rescue analgesia, nausea or patients satisfaction during the first 24 postoperative hours.</p> <p>Conclusion</p> <p>Coxib premedication before elective day surgery has an anaesthetic sparing potential.</p

A Bovine Model of Respiratory Chlamydia psittaci Infection: Challenge Dose Titration

This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2–3 months via bronchoscope at four different challenge doses from 106 to 109 inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 106 ifu/calf resulted in a mild respiratory infection only, the doses of 107 and 108 induced fever, tachypnea, dry cough, and tachycardia that became apparent 2–3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 109 ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 106 and 107 ifu, about 15% in calves inoculated with 108 and more than 30% in calves inoculated with 109 ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 106 or 108 ifu/calf of C. psittaci DC15 while doses above 108 ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host-pathogen interactions

Portable respiratory polygraphy monitoring of obese mothers the first night after caesarean section with bupivacaine/morphine/fentanyl spinal anaesthesia [version 2; referees: 2 approved]

Background: Obesity, abdominal surgery, and intrathecal opioids are all factors associated with a risk for respiratory compromise. The aim of this explorative trial was to study the apnoea/hypopnea index 1st postoperative night in obese mothers having had caesarean section (CS) in spinal anaesthesia with a combination of bupivacaine/morphine and fentanyl. Methods: Consecutive obese (BMI >30 kg/m 2) mothers, ≥18 years, scheduled for CS with bupivacaine/morphine/fentanyl spinal anaesthesia were monitored with a portable polygraphy device Embletta /NOX on 1st postoperative night. The apnoea/hypopnea index (AHI) was identified by clinical algorithm and assessed in accordance to general guidelines; number of apnoea/hypopnea episodes per hour: 5. Mothers with a high AHI (15.3 and 18.2) did not show high ODI. Mean saturation was 94% (91-96%), and four mothers had mean SpO2 90-94%, none had a mean SpO2 <90%. Conclusion: Respiratory polygraphy 1st night after caesarean section in spinal anaesthesia with morphine in moderately obese mothers showed AHIs that in sleep medicine terms are considered normal, mild and moderate. Obstructive events and episodes of desaturation were commonly not synchronised. Further studies looking at preoperative screening for sleep apnoea in obese mothers are warranted but early postop respiratory polygraphy recording is cumbersome and provided sparse important information

Neuraxial opioids as analgesia in labour, caesarean section and hysterectomy: A questionnaire survey in Sweden [version 2; referees: 2 approved]

Background: Neuraxial opioids improve labour analgesia and analgesia after caesarean section (CS) and hysterectomy. Undesirable side effects and difficulties in arranging postoperative monitoring might influence the use of these opioids. The aim of the present survey was to assess the use of intrathecal and epidural morphine in gynaecology and obstetrics in Sweden. Methods: A questionnaire was sent to all anaesthetic obstetric units in Sweden concerning the use and postoperative monitoring of morphine, sufentanil and fentanyl in spinal/epidural anaesthesia. Results: A total of 32 of 47 (68%) units responded representing 83% of annual CS in Sweden. In CS spinal anaesthesia, 20/32 units use intrathecal morphine, the most common dose of which was 100 μg (17/21). Intrathecal fentanyl (10-20 μg) was used by 21 units and sufentanil (2.5 -10 μg) by 9/32 of the responding units. In CS epidural anaesthesia, epidural fentanyl (50-100 μg) or sufentanil (5-25 μg) were commonly used (25/32), and 12/32 clinics used epidural morphine, the majority of units used a 2 mg dose. Intrathecal morphine for hysterectomy was used by 20/30 units, with 200 μg as the most common dose (9/32). Postoperative monitoring was organized in adherence to the National Guidelines; the patient is monitored postoperative care or an obstetrical ward over 2-6 hours and up-to 12 hours in an ordinary surgical ward. Risk of respiratory depression/difficult to monitor was a reason for not using intrathecal opioids. Conclusions: Neuraxial morphine is used widely in Sweden in CS and hysterectomy, but is still restricted in some units because of the concern for respiratory depression and difficulties in monitoring

The decision to delivery interval in emergency caesarean sections: Impact of anaesthetic technique and work shift [version 1; referees: 2 approved]

Background: One important task of the emergency anaesthesia service is to provide rapid, safe and effective anaesthesia for emergency caesarean sections (ECS). A Decision to Delivery Interval (DDI) <30 minutes for ECS is a quality indicator for this service. The aim of this study was to assess the DDI and the impact of chosen anaesthetic technique (general anaesthesia (GA), spinal anaesthesia (SPA) with opioid supplementation, or “top-up” of labour epidural analgesia (tEDA) with local anaesthesia and fentanyl mixture) and work shift for ECS at Danderyds Hospital, Sweden. Methods: A retrospective chart review of ECS at Danderyds Hospital was performed between January and October 2016. Time between decision for CS, start of anaesthesia, time for incision and delivery, type of anaesthetic technique, and time of day, working hours or on call and day of week, Monday – Friday, and weekend was compiled and analysed. Time events are presented as mean ± standard deviation. Non-parametric tests were used. Results: In total, 135 ECS were analysed: 92% of the cases were delivered within 30 minutes and mean DDI for all cases was 17.3±8.1 minutes. GA shortened the DDI by 10 and 13 minutes compared to SPA and tEDA (p<0.0005). DDI for SPA and tEDA did not differ. There was no difference in DDI regarding time of day or weekday. Apgar <7 at 5’ was more commonly seen in ECS having GA (11 out of 64) compared to SPA (2/30) and tEDA (1/41) (p<0.05). Conclusion: GA shortens the DDI for ECS, but the use of SPA as well as tEDA with opioid supplementation maintains a short DDI and should be considered when time allows. Top-up epidural did not prolong the DDI compared to SPA. The day of week or time of ECS had no influence on the anaesthesia service as measured by the DDI

Elastosis perforans serpiginosa related to vascular Ehlers-Danlos syndrome

Elastosis perforans serpiginosa (EPS) is a rare skin disease with elimination of connective tissue fibers from dermis to epidermis. The typical presentation shows hyperkeratotic red or skin-colored papules arranged in a circinate pattern. We present a 26-year-old woman with EPS known to have vascular Ehlers-Danlos syndrome

Elastosis perforans serpiginosa related to vascular Ehlers-Danlos syndrome

Elastosis perforans serpiginosa (EPS) is a rare skin disease with elimination of connective tissue fibers from dermis to epidermis. The typical presentation shows hyperkeratotic red or skin-colored papules arranged in a circinate pattern. We present a 26-year-old woman with EPS known to have vascular Ehlers-Danlos syndrome

Elastosis perforans serpiginosa related to vascular Ehlers-Danlos syndrome

Elastosis perforans serpiginosa (EPS) is a rare skin disease with elimination of connective tissue fibers from dermis to epidermis. The typical presentation shows hyperkeratotic red or skin-colored papules arranged in a circinate pattern. We present a 26-year-old woman with EPS known to have vascular Ehlers-Danlos syndrome