Porcine influenza

H1N1 is everywhere now and we're all pretty sanguine about it. But pregnancy appears to be a real risk factor for serious morbidity and mortality. We should have it on the differential diagnosis list for pregnant women with premature labour with fever: it may not be chorioamnionitis. Pregant contacts of flu cases should be given osteltamivir, and the pregnant woman with flu symptoms should be closely watched for worsening pneumonia.

F%&*!2! Fentanyl!

Ever since I started practising anaesthesia in 1991 fentanyl has been part and parcel of almost every anaesthetic I have given or observed. At the very least 50 – 100 mcg is used to attenuate the airway and cardiovascular response to airway management. More fentanyl can be used for further intraoperative analgesia and sometimes it becomes a total fentanyl affair with PCA continued postoperatively. Even neuraxial anaesthesia usually has fentanyl as part of it.

But it seems this potent µ receptor could be causing underappreciated trouble. The potent lipophilic opioid agonists (fentanyl, remifentanil etc) induce acute opioid tolerance which results in more severe postoperative pain which is more resistant to morphine analgesia.

This phenomenon has been well studied in rats using doses (per body mass) that are far in excess of human clinical practice and it seems it is due to changes that occur in the NMDA and GABA receptor processes.

But even modest clinical doses in humans seem to contribute to this unwanted effect. Sukhani (Anesthesia-Analgesia Nov 1996) compared anaesthesia for gynaecologic laparoscopy with 100mcg fentanyl versus 15 – 30 mg ketoralac without fentanyl. Pain, nausea and time to discharge was longer in the 100 mcg fentanyl group even though this group had lesser intraoperative propofol.

In a more contemporaneous technique, anaesthesia for laparoscopic cholecystectomy was compared by Collard in Anesthesia-Analgesia (Nov 2007). Desflurane anaesthesia was administered with either fentanyl, esmolol or remifentanil. The esmolol group had the superior postoperative course with significantly less need for analgesia and antiemesis and a more rapid discharge. The remifentanil group had the worse outcomes for analgesia, emesis and discharge time.

Remifentanil may not be the wonder “nitrous-oxide killer” after all. The literature now abounds with the effect of remifentanil on morphine tolerance and hyperalgesia and a report of its use for a laparoscopy (Rev Esp Anestesiol Reanim. 2008 Jan;55(1):40-2) reports an extreme case of postoperative hyperalgesia.

Morphine, presumably because of its lesser potency and lipophilicity does not cause such a degree of rapid acute tolerance, but of course its tendency to cause PONV still limits in applicability in some situations.

Ketamine seems to counter the acute tolerance of the lipophilic opioids and I wonder if this is what its true analgesic effect is. It may be better avoiding lipophilic opioids altogether and using anaesthetics (including regional anaesthesia and intravenous lignocaine) to anaesthetise and alpha and beta blockers to attenuate haemodynamic stress. Perhaps analgesics should be kept in reserve until pain is expressed or soon before pain is expected to be expressed.

At the ANZCA ASM: consequences of liberal opioid prescription

Steven Passik, a New Yorker who spoke and entertained like Jerry Seinfeld, related the huge public health consequences of the liberalisation of opioid prescription in the US over the last decade. Oxycodone and hydromorphone abuse has become rampant, not so much by the patients for who it was prescribed, but among the friends, family and customers who get their hands on the dispensed drugs as well.

His suggestions were more for those who manage chronic pain patients, but his words made me think we should be even more cautious in the size of our postoperative opioid dispensations for discharged patients. Are 20 tablets of whatever really needed?

25G Whitacre and headache: reassuringly rare enough

A neat little audit report from Preston, Lancashire in Anaesthesia Jan 09. Martlew reports a 9 year audit of spinal anaesthesia for caesarean section. They used 25 G Whitacre needles and changed over the years from no opioid, then adjunctive fentanyl, and finally diamorphine. They think diamorphine reduced the risk of headache from 1.4% without diamorphine to 0.49% with diamorphine.

The curious stat for this Australian who uses bupivacaine with fentanyl is that this mixture through a 25 G Whitacre needle gave a headache rate of 0.88%. One blood patch was used in 1022 patients.

So while the finer 27 G might seem the preferred needle, in circumstances of haste or difficulty the more robust 25 G needle is an appropriate alternative.

Multimodal confusion

Kevin Rudd likened the GFC to a faecal meteorological event and the recent exposure of Scott Reuben as a fraudster warrants the same analogy. Reuben's publications have encouraged the use of NSAIDs, COX2 inhibitors, clonidine and controlled release oxycodone in the perioperative acute pain setting, and their use have been encouraged by authoritative guidelines. But it could be all back to square one for the clinical science of acute pain, particularly as the association of NSAIDs and COX2Is with a range of harmful effects make their use difficult to justify without good evidence.
We await the editorials in the May edition of Anesthesia Analgesia.

Relax about the thromboprophylax

Clin Pharmacol Ther. 2008 Sep;84(3):370-7. has an interesting article on the pharmacokinetics of enoxaparin in pregnancy. Basically, the clearance of enoxaparin greatly increases during the course of pregnancy resulting in a marked decrease in anti-Xa activity. The authors even recommend that thromboprophylaxis should be dosed to the pregnant patient's weight rather than a standard 40 mg/day.

What I find curious about this graph I trapped on my mobile phone (no online version available) is that the peak level in late pregnancy (the dark line) is the same level as the 12 hour point for non-pregnancy. Guidelines warn us off CNBs for 12 hours after 40 mg enoxaparin, but in pregnancy the anti-Xa level at the 4 hour peak is the same as when the level is presumed safe in the non-pregnant safe.

So if the parturient has recently had a standard 40 mg enoxaparin, is it reasonable to offer an epidural or spinal? If no, the poor soul will be denied the benefits of an obstetric regional analgesia/anaesthesia as well as being managed with sub-therapeutic thromboprophylaxis!

FAB for CNB

The BJA in "Advanced Access" publishes Major complications of central neuraxial block: report on the Third National Audit Project of the Royal College of Anaesthetists. In brief, its conclusions are reassuring. The absolute risk of CNB is low, but is relatively higher for perioperative use compared to obstetric use. In obstetrics, the risk of a major complication of CNB is extremely low, but curiously (and unsurprisingly!) CSE is given a higher rate compared to both spinal and epidural. In the perioperative group, spinal is given a much lower rate than both epidural and CSE. This audit sought severe complications. One wonders if less severe, but troublesome complications such as neuropathy and headache have similar comparitive rates of relative risk between the clinical groups and types of CNB.

As a practice implication, for me this report reinforces that epidural alone is the choice technique for a routine request for "an epidural" in labour, and spinal anaesthesia is the choice for routine caesarean section in an uncomplicated parturient. In the perioperative setting, this report reinforces an advantage of intrathecal opioid via a spinal needle compared to epidural catheter infusion of anaesthetic and opioid for postoperative analgesia.

Gimme oxygen

Van de Velde in this month's BJA editorial sums up what should be common sense, albeit without an evidence base until the accompanying article in the same volume: supplementary oxygen for the emergency caesarean, but not needed for the elective one.

Midazolam: pro or con

Midazolam is a near default drug when it comes to Australian anaesthesia, even for brief procedures with propofol. A survey by Padmanabahn and Leslie (Anaesthesia & Intensive Care, May 2008) reported that 75% of respondents use midazolam with propofol, and usually with fentanyl.

But for brief procedures like endoscopy, local anaesthetic surgery, oocyte retrieval, and curetttage it seems there is usually no value in using midazolam in the induction of sedation/anaesthesia, and indeed it only slows the time to full recovery. The endoscopy literature has a lot of comparisons between propofol and midazolam which demonstrate this, and that will not surprise most. Seifert and others (Aliment Pharmacol Ther 2000; 14: 1207±1214.) looked at the use of midazolam with propofol versus propofol alone for ERCP. A mean of 2.9 mg midazolam was used when it was used, and the recovery to clear conversation those patients was 6 minutes longer and the PARS was better in the propofol alone group even at 30 min. There were no differences in recall or the tolerating the ERCP.

Although a difference of minutes may not seem much from the perspective of the individual patients care, these types of cases are often clustered in sizeable groups which can place quite a demand on a facility and its staff. Even if midazolam only contributed an average of an extra 20 minutes for patients to walk out the door it means that a busy facility that deals with, say, 15 of these cases has 300 extra patient-minutes on the recovery trolleys and chairs, but with no measureable intraoperative benefit. The ampoule of midazolam can be quite expensive.