34 year old female who is 15 weeks pregnant for cerclage

A 34 year old female required cerclage for incompetent cervix and presented to the OR for the procedure.  I discussed the pros and cons of GA vs. regional neuraxial anesthesia and we proceeded with spinal anesthesia.  The patient was taken to the OR, 6.5mg of hyperbaric bupivacaine + 20 mcg fentanyl was administered via 25 G whitakre needle.  The patient remained seated for aproximately 1 minute and then was layed supine. The patient tolerated the procedure without sedation.

The patient went to PACU able to move her legs but complaining of sinificant pruritis for which she requested treatment.  She was discharged after  2 hours and 37 min in the PACU after a case that was 30 min in duration.  

Management of the pregnant patient brings about a lot of questions for the anesthesiologist. Determining what anesthetics are safe and if needed what can be used to treat common side effects of anesthesia must be considered.  For example, in our patient, pruritis is typically treated with benadryl.  This medication may not be appropriate for the parturient however.  In general, I prefer to provide spinal anesthesia for cerclage. While there is currently no evidence to indicate that anesthetics are teratogenic, there is a growing literature demonstrating that anesthetics are neurotoxic to the fetus or early developing brain. While large human studies in pediatric patients seem to indicate that there is no significant increased risk to the brain, we have no good studies to indicate that there is not alteration to neurogenesis in the fetus.  Furthermore, even though we do not have evidence of harmful fetal affects of anesthetics, we also lack good solid randomized controlled trials to prove an absence of negative effects.  If you perform an anesthetic on a patient who is pregnant who goes on to deliver a newborn with obvious defects, not otherwise explained, you carry potential legal risk unless you can establish that general anesthesia was truly your only option.  

Giving spinal anesthesia to a patient who is to be discharged the same day creates panic in surgeons and facility administrators who are convinced that the patient will require prolonged care due to inability to void.  Therefore, in some cases overcoming this concern can be prohibitive.  Avoiding prolonged PACU stays (due to post operative urinary retention [POUR]) is accomplished by modification of typical intrathecal doses.

POUR-

The control of micturition is a complex process involving multiple afferent and efferent neural pathways, reflexes and central and peripheral neurotransmitters.  It is well known that bupivacaine and tetracaine delay return of bladder function beyond the resolution of sensory anesthesia, and may lead to distention of the bladder beyond its normal functioning capacity.  This may result in bladder damage. The normal bladder has a capacity of between 400 mL and 600 mL.  The detrusor muscle is innervated by efferent somatic, sympathetic and parasympathetic fibers.  The parasympathetic fibers cause contraction of the detrusor and relaxation of the spinchter, permitting micturition. The sympathetic fibers produce detrusor relaxation and internal urethral sphincter closure.  The two systems are governed by spinal reflexes and two pontine brain stem centers. General anesthesia casues bladder atony. Volatile anesthetics as well as sedative-hypnotics inhibit  the pontine micturition center and voluntary cortical control center of the bladder.  IT injection of bupivacaine will block afferent and efferent neural transmission from and to the spinal segments (S2-S4).   Typically, complete normalization of detrusor strength occurs 1 to 3.5 h after ambulation. IT injection of opioid decreases the urge sensation and detrusor contraction largely by opioid effect on opioid receptors in the spinal cord that decrease parasympathetic firing.  Theses effects as well as others, can be reversed with naloxone administration. It is understood that opioids added to IT local anesthetic increases the rate of POUR.   This concept was looked at in an article by Niazi et al. [1].  They compared three groups of patients who received hyperbaric bupivacaine 0.5% (15 mg) (S1), bupi 15 mg + fentanyl 20 mcg (S2) or GA (G).  The incidence of POUR was 20% in group S1, 35% in group S2, and 8% in group G.  There incidence of 35% of POUR in the local + fentanyl group was much higher than another study [2] where the group with fentanyl given IT had POUR of only 20%.  This is likely because in this study only 7.5 mg of bupivacaine was used and 25 mcg of fentanyl.  The impact of bupivacaine dose was considered in a study that compared bupivacaine with lidocaine for spinal anesthesia for cervical cerclage.  In this study, the bupivacaine dose was 5.25 mg with 20 mcg of fentanyl added.  This was compared to lidocaine 30 mg + fentanyl 20 mcg [3]. They did not detect any difference between the two anesthetics with regard to onset and recovery time. They concluded that low dose bupivacaine (5.25 mg) offered a similar recovery profile to lidocaine IT 30 mg.  They did have 2 of 30 women in the lidocaine group with complaints consistent with TNS that resolved in 48 hours.  Indeed, lidocaine is really the gold standard in regards to outpatient spinal anesthesia.  Due to its reputation of causeing TNS, it has fallen into disuse.  TNS or transient neurological symptoms is described as transient buttock pain, radicular lower extremity pain, and dysesthesias that present within the first 24 hours following recovery from spinal anesthesia.  Some have reported an incidence as high as 40% with lidocaine. There is also some who speculate that the hyperbaric lidocaine solution (5% hyperbaric could be the cause) of TNS.  A recent study of  50 patients using 2% isobaric lidocaine as a single IT dose did not find a single case of TNS [4].  Unfortunately, this paper did not disclose the lidocaine dose.  This is important, because some studies suggest that the incidence of TNS is dose dependent [6].  In fact, some research or analysis of research suggests that using a lidocaine dose of less than 25 mg might prevent TNS from lidocaine.  The above study failed to cite another study performed in 1998 (Anesthesiology [5]). In this publication isobaric lidocaine 60 mg at a 2% concentration was compared to mepivacaine 1.5 %.  They found a 22.2% incidence of TNS with this formulation of lidocaine vs 0% in the mepivacaine group.  Another group used 10 mg lidocaine for spinal anesthesia and found a 0% incidence of TNS [7] with good operating conditions for prostate bx.  Another group compared knee arthroscopy in patients who received IT unilateral  bupivacaine 3 mg + fentnayl 10 mcg vs bilateral lidocaine 20 mg + fentanyl 25 mcg [8].  In this study no patients in either group suffered TNS (each group had n=25).  The incidence of pruritis was 5/25 patients and 7/25 patients in the bupi group vs the lido group.  Urinary retention not requiring bladder catheterization was found in 2/25 patients in the bupivacaine group (however the p value was 0.149).  They reported 100% excellent operating conditions for knee arthroscopy, with a duration of sensory block of 157 min in the bupivacaine group and 129 min in the lidocaine group. Time spent in the PACU was 39 min vs 0 min in the bupivacaine vs lidocaine group, time to ambulate was 159 min vs 3.6 min and time to home readiness was 184 min vs 153 min in the bupivacaine vs lidocaine group respectively.  while this was a small study, it seems to emphasize that with 20 mg of lidocaine + fentnayl, you can achieve a very short PACU stay, nominal risk for urinary retention, with very low chance of TNS.  Unfortunately, in many institutions, spinal lidocaine is simply not available.  Therefore, low dose bupivacaine is an alternative.  I opted for 6 mg of bupivacaine, but as mentioned there is some evidence that 5.25 mg of bupivacaine is sufficient for cerclage.  

1.  Niazi AAA, Taha MAA. Egyptian Journal of Anesthesia. 2015. 31:65-9.

2. Gupta A, Axelsson K, Thorns, E, et al. Acta Anaesthesiol Scand 2003;47:13-9.

3. Beilin Y, Zahn J, Abramovitz S, Bernstein HH, Hossain S, Bodian C.  Anesth Analg. 2003; 97: 56-61.

4. Frisch NB, Darrith B, Hansen DC, Wells A, Sanders S, Berger RA. Arthroplast Today. 2018;4:236-39.

5. Liguori GA, Zayas VM, Chisholm MF. Anesthesiology 1998. 88; 619-23.

6. Buckenmaier CC III, Nielsen KC, Pietrobon R, et al. Anesth Analg 2002;95:1253-7.

7. Nishikawa K. et al. Jour of Clinical Anesthesia 2007;19:25-9.

8. Hassan HIEA, Anesth Essays Res 2015. 9:21-27.

26 year old on TPN for major bowel surgery

A 26 year old female with previous bowel surgery for superior mesenteric artery (SMA) syndrome, presents to have a revision of her gastrojejunal anastomossis.  SMA syndrome occurs when the aorta and superior mesenteric artery wrap around the duodenum in such a way as to compromise the passage of food through the narrowed part. The syndrome is often related to loss of the mesenteric fat pad in the area. In this case the patient suffered from anxiety and a history of anorexia nervosa likely leading to the loss of the mesenteric fat pad. During two previous abdominal surgeries the patient suffered complications of post operative pain unrelieved by post operative thoracic epidural analgesia and multimodal analgesia.  She was also persistently nauseous and struggled to tolerate food post op.  She had to return to the OR a second time due to the development of a stricture post op in her small intestine.  The second surgery also resulted in a similar challenge of pain control with severe nausea.  The patient is now scheduled for a third surgery, a revision gastrojejunal anastomosis and gastrojejunostomy.

Given that the patient is very likely to suffer as in her prior surgeries with significant pain, I have decided to consider an aggressive multimodal pain regimen for post op pain.  Currently, many surgeons are requesting transversus abdominal pain blocks (often with catheters) for post op pain control after abdominal surgery.  In many cases, it appears that this method of pain control is supplanting TEA as the primary regional technique for pain control after abdominal surgery.  Unfortunately, I have had less success with the TAP technique for open abdominal surgery in particular with upper (above the umbilicus) abdominal surgery.  It is well known that the transverses abdominal plane block (TAP) provides somatic analgesia to the skin and anterior abdominal wall. Unfortunately, pain sensation from the viscera and peritoneum are not blocked with this technique as it is with epidural analgesia (EA).  Recently a head to head trial comparing TAP vs EA was published [1].  The authors found that in lower abdominal surgery, TAP had similar pain control to EA patients for the first 16 hours.  After 16 hours up to 48 hours, the group with epidural analgesia had better pain control.  For incisions above the umbilicus, it is recommended that a subcostal technique be used.  However, for long incisions, it is often difficult to get enough spread of local anesthetic in the transversus abdominis plane to block all of the necessary nerves. Nevertheless, Rao et al. were able to show that after major abdominal surgery, TAP catheters were equal to EA in terms of pain scores, opioid requirements, and patient satisfaction [2]. In another study of open laparotomy patients (n=51)[3], Ganapathy et al. found that TAP catheters were essentially equivalent to EA during 72 hours in terms of pain control. However, in another study, TAP catheters were inferior to EA for pain control after major open abdominal surgery [4].  A small meta analysis of four studies was unable to find any significant differences in pain control or opioid use after abdominal surgery when comparing TAP catheters with EA [5].  However, there was a trend toward increased morphine use in the TAP catheter group.  All, in all, it would appear that  for abdominal surgery TAP catheters can be a reliable alternatively to EA when pain control is the only outcome of interest. However, multiple studies and a cochrane review have shown that for the important endpoint of reduction in post operative ileus, EA is helpful.  (see here for cochrane review). In this particular case, post operative ileus is a major concern.  The patient is currently on TPN, due to continued poor oral intake.  It will be imperative to maximize her chances of avoiding a prolonged post operative ileus.  Therefore,  EA would be an ideal choice.  However, this patient is likely to still have significant post operative pain as she did after her prior two abdominal surgeries despite having a functioning thoracic epidural.  There is evidence that in patients with difficult to treat pain, that ketamine can be helpful.  There is a large literature related to ketamine use in the perioperative period. In 2010, a Cochrane review found that sub-anesthetic ketamine reduced analgesic requirements and/or pain scores in 27 of 37 RCTs [10].  Currently, most guidelines suggest giving a bolus of 0.5 mg/kg at the beginning of the case plus an infusion of 0.25mg/kg/hr during surgery.   De Koch et al. found that intraoperative ketamine  ( 0.5 mg/kg bolus + 0.25 mg/kg/hr infusion) reduced morphine consumption in patients having abdominal surgery [6].  Importantly, this occurred even though all patients received aggressive EA.  Furthermore, they were able to show that secondary hyperalgesia was reduced in the ketamine group and that in this group, chronic post operative pain was significantly less at 6 months after surgery.  Himmeslseher et al. published a meta analysis on ketamine for post operative pain control.  They recommend ketamine to reduce post operative pain and provided the following recommendations:

Major surgery:  0.5 mg/kg bolus prior to incision and 0.5 mg/kg/hr infusion until end of surgery. then post op infusion of 0.12 mg/kg/hr x 24 hours in the post operative period.

Minor surgery: 0.25 mg/kg bolus prior to incision + 0.25 mg/kg/hr infusion until the end of surgery.

Dosages above are fairly aggressive, and it is clear that post operative hallucinations, vivid dreams and other cognitive affects are more frequent and more severe at higher doses.  Therefore, I tend to decrease the doses from those recommended above.

Multipmodal analgesia will be very important so I will given IV Tylenol during the surgery and then q 8 hours post op.

 Another option is an IV infusion of Magnesium.  Magnesium as an adjunct for pain control has been considered for decades.  A large number of clinical studies looking at the use of magnesium for post operative pain control have been published with mixed results.  A systematic review in 2007 that included 14 studies could not detect a beneficial effect of systemic magnesium administration on post operative pain control [8].  In 2013, another systematic review was undertaken and was able to demonstrate a beneficial effect of magnesium on pain control [9].  The largest improvement was the reduction in morphine consumption as noted in the figure below.  Most of the studies utilized a 30 mg/kg bolus or a 50 mg/kg bolus +/- an infusion of  between 8 mg/kg/hr to 15 mg/kg/hr intraoperatively or a few even post operatively.

Fig 1 post operative morphine consumption is reduced with magnesium.

Magnesium acts as an NMDA antagonist to reduce the perception and duration of pain.

Recently, more and more groups have started to take interest in the possibility of gabapentin reducing post operative pain and/or analgesic opioid requirements. In 2013, an article in Anesthesiology stated that the current evidence suggested that gabapentinoids (gabapentin and pregabalin) could reduce preoperative acute pain/analgesic requirements and the incidence of post surgical chronic pain development.

gabapentinoid pharmacology: these are not active at the GABA-a receptor although they are GABA structural analgues.

These GABA analogues actually bind to the alpha 2-delta subunit of pre synaptic P and Q type voltage gated calcium channels.  Doesn't make much sense, but that's how they cause the effect we are looking for. This is believed to modulate the release of excitatory neurotransmitter from activated nociceptors. So, by inhibiting Calcium induced release of glutamine, these agents can inhibit pain transmission and/or decrease central sensitization.  Alternatively, some evidence indicates that their antinociceptive mechanism may arise through activation of noradrenergic pain-inhibiting pathways in the spinal cord and brain. (see figure)

In 2016 a meta analysis of gabapentinoids [11] in dosages from 300 mg to 1200 mg found that they were helpful in reducing morphine consumption for the first 24 hours after surgery.  They did report increased sedation levels in patients who received gabapentinoids, and there was no decrease in side effects such as pruritus, nausea or vomiting.  Two different studies looked at gabapentin as a part of a multimodal analgesia program and both concluded that it was of questionable benefit in this context. The first of these two studies was a RCT in TKA with gabapentin [12].  In this study patients were given 600 mg gabapentin preop with 200 mg q8 hours post op along with morphine, ketorolac and tylenol.   Morphine consumption and VAS scores were similar between groups.  Monks et al. [13] looked at gabapentin in post cesarean section patients at dose of 600 mg preop and 200 mg q8 hours post op. Patients received spinal morphine. There was a very slight decrease in morphine consumption in the group receiving gabapentin and the authors concluded that gabapentin is of questionable benefit in cesarean section patients.  One consideration that is important is to understand that gabapentin is an oral medication and was not possible to use in our case in a patient requiring TPN due to an inability to tolerate oral intake.  In addition, I was planning an aggressive multimodal pain program to include regional anesthesia, toradol, tylenol IV, magnesium infusion and a ketamine infusion, thereby making gabapentin an unlikely success in further reducing post op pain scores or opioid consumption.

One day prior to the scheduled surgery the pre admissions testing nurse called me to report that the patient had a lab drawn and that her potassium was 2.9 mEq/L. The nurse at the PAT clinic reported that the patient had a PICC line where she receives TPN in addition to potassium replacement.  The nurse also revealed that the patient suffers from orthostatic hypotension for which she is prescribed midorine and fludrocortisone.  I instructed the nurse to call the patient and have her stop her fludrocortisone the day before surgery and to come in early for repeat K+ lab draw with an order to start 20 mEq of postassium if her K+ level was below 3.1 mEq/L.

Orthostatic hypotension is often caused by failure of the autonomic nervous system. There are a variety of reasons for failure of the autonomic nervous system including:

• Multiple system atrophy
• familial dysautonomia
• dementia with lewy bodies
• Shy-Drager's syndrome
• Parkinson's disease
• longstanding diabetes
• Vitamin deficiencies (our patient)
• Amyloidosis
• Bronchogenic carcinoma
• Pure autonomic failure

Treatment for othorstatic hypotension can include a direct vasocontrictor.  My patient was taking midodrine, which is a prodrug and acts on the alpha 1 adrenergic receptor to cause vasoconstriction. Unfortunutely, this can lead to supine hypertension that is severe in some patients. This supine hypertension can result in pressure natriuresis leading to a worsening of orthostatic hypotension.  In patients taking midodrine for autonomic failure, there is typically an associated denervation hypersensitivity making these patients exquisitely sensitive to norepinephrine.   Patients with autonomic failure have other clinical manifestations as well.  These may include post prandial hypotension, urinary bladder dysfunction leading to urinary retention, and decreased gastrointestinal motility.

Fludrocortison is a mineralocorticoid used in patients with orthostatic hypotension.  It results in fluid retention and patients often will gain 2 to 3 Kg of water weight before receiving full benefit of this medication. Fludrocortisone does have some  glucocorticoid activity above dosages of 0.3 mg per day and this must be considered as to whether the HPA axis may be inhibited.  Mineralocorticoids act by mimicking aldosterone (binding to the aldosterone receptor in the cell necleus) which causes sodium retention at the expense of excretion of potassium and hydrogen ions. The action occurs in the renal collecting tubules.   This can lead to severe hypokalemia and metabolic alkalosis.  In addition, about 10% of patients also suffer from hypomagnesemia with chronic fludrocortisone therapy.  Because fludrocortisone does have some glucocorticoid activity, I could not ensure that the patient's HPA axis was not suppressed, and therefore, in addition to 4 mg of dexamethosone (purely glucocorticoid activity) I gave a one time dose of solucortef 50 mg.  This medication has both glucocorticoid and mineralocorticoid activity. 

On the day of surgery the patient arrived and a repeat potassium level came back at 3.3 mEq/L. Therefore, KCL infusion was not required prior to proceeding as I was worried might happen.  As discussed above, there is evidence that EA and bilateral subcostal TAP catheters are equivalent.  It was decided to proceed with GETA and post operative placement of subcostal TAP catheters.  The patient weight was 50 kg.  The patient was given 2 mg of versed and 2 mg of dilaudid and we rolled to the OR.  Induction was with propofol and rococuronium.  The patient was given ketamine in 25 mg increments to a total of 100 mg.  She was given MgSO4 2 GM intraoperatively, and another 1 GM was infused post operatively.  She also received decadron 4 mg, solocortef (to add some mineralocorticoid activity) 50 mg, IV tyelonol 1000mg, and zofran 4 mg.  The open laparotomy with revision of gastrojejunal anastomosis was uneventful and the patient arrived in the PACU extubated and breathing comfortably.  After 30 min the patient was interviewed and complained of 8/10 pain.  The nurse administered opioid pain medications.  A post operative ketamine infusion was begun at 5 mg/hr with a magnesium infusion of 250 mg/hr.  She received an additional amount of magnesium in her TPN solution.  The surgeon also prescribed a PCA with hydromorphone.  On POD 1, the patient appeared comfortable in her bed but complained of 8/10 pain.  It should be noted that on the first night on the day of surgery, the nurses called me to tell me that the patient had respiratory depression and that they had d/c'd all of her pain medications until she woke up.  It was decided to restart her magnesium and ketamine infusion, and cut her hydromorphone dose in half.  The patient requested EA, however, the surgeon intervened to avoid this.  The patients was NPO and therefore, not receiving fludrocortisone or midodrine, both oral medications.  Her blood pressures were low normal.

In this case, EA is likely to have been a better choice than TAP catheters.  Particularly on POD 1 when it became apparent that the patient had an event of respiratory depression from opioids requiring adjustment of the medication.  In addition, the patient perceived that her pain control was not adequate nor being addressed.  She stated that the TAP catheters were not working.  A test with ice to the skin around the incision was unable to detect any decrease in sensation or perception of cold.  This is a fairly good indicator of failure of block.  I have a long experience with the placement of TAP catheters and doing the subcostal block.  This patient was thin, and the US guided block went flawless, with excellent landmarks that were well visualized. However, the subcostal approach relies on local anesthetic spreading throughout the transversus abdominis plane and finding the nerves as they run along to their destination.  The actual nerves are not visualized and it is impossible to guarantee that all of the nerves will be bathed in local anesthetic (LA).  This is also true for EA, however.  The patient did state that the block was patchy.  To me this indicated that indeed the LA was located around several nerves, but that there were others not reached by the LA. This, to me constitutes a general weakness of the TAP approach than my technique.  On POD 2 the patient appeared much more comfortable and in fact had reduced the amount of opioid pain medication she was consuming.






1. Sadasivan Shankar Iyer, Harshit Bavishi, Chadalavada Venkataram Mohan, and  Navdeep Kaur,  Anesth Essays Res. 2017 (11)7: 670-675

2. Rao Kadam V, Van Wijk RM, Moran JI, Miller D. Anaesth Intensive Care. 2013;41:476–81.

3. Ganapathy S, Sondekoppam RV, Terlecki M, et al. . Eur J Anaesthesiol 2015;32:797–804

4. Wahba SS, Kamal SM. . J Anesth 2014;28:517–23.

5. Zhang P, Deng XQ, Zhang R, Zhu T.  Br J Anaesth. 2015;114:339. 

6.  De Kock M, Lavand'homme P, Waterloos H.  Pain 92(2001) 373-380.

7. Himmeslseher S, durieux ME. Ketamine for perioperative Pain Management. Anesthesiology. 2005; (102):211-20.

8.  Lysakowski, C, Dumont, L, Czarnetzki, C, Tramèr, MR . Anesth Analg. (2007). 104 1532–9 

9. Gildasio S. De Oliveira, Jr, M.D., M.S.C.I.; Lucas J. Castro-Alves, M.D.; Jamil H. Khan, B.S.; Robert J. McCarthy, Pharm.D. Anesthesiology 07 2013, Vol.119, 178-190

10. Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2006

11. Sudha Arumugam, Christine SM Lau, and  Ronald S Chamberlain. J Pain Res. 2016; 9: 631–640.

12. Paul JE, Nantha-Aree M, Buckley N, Cheng J, Thabane L, Tidy A, DeBeer J, Winemaker M, Wismer D, Punthake D, Avram V; Gabapentin does not improve multimodal analgesia outcomes for total knee arthroplasty: a randomized controlled trial; Canadian Journal of Anesthesia 2013, 60:423-431

13. Monks DT, Hoppe DW, Downey K, Shah V, Bernstein P, Carvalho JCA; A perioperative dose of gabapentin does not produce a clinically meaningful improvement is analgesia after cesarean delivery; Anesthesiology 2015 August, 123(2): 320-326