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Abstract

Background:

Radical cystectomy (RC) is the gold standard therapy in nonmetastatic muscle-invasive bladder cancer and is usually performed under general anesthesia (GA). GA is high risk in most older patients due to comorbidities. Continuous spinal anesthesia (CSA) may be an alternative solution to reduce postoperative morbidity in elderly. The aim of this study was to assess the feasibility, morbidity, and mortality of RC performed under CSA in octogenarian patients.

Methods:

We retrospectively reviewed data of five frail patients aged ⩾80 who underwent RC in CSA. CSA was achieved starting with 2.5 mg hyperbaric bupivacaine plus 25 µg fentanyl. Postoperative analgesia was achieved through the intrathecal catheter, using continuous delivery of levo-bupivacaine 60 mg plus fentanyl 75 µg in 72 hours.

Results:

Surgery was completed in all cases in CSA. No patients required postoperative intensive care unit admission. Complications were Clavien I for four in three patients, Clavien II for seven in five patients, and Clavien IIIb for one patient. Postoperative consumption of painkillers was negligible. Oral feeding resumed within 3 days in all cases. The mean postoperative stay was 9.6 days. All patients were alive at 3 months of follow up.

Conclusions:

Management of muscle-invasive bladder cancer (MIBC) in older patients is becoming an important issue due to the continuous aging of the population. Age should not preclude RC, but careful management is mandatory because perioperative morbidity and mortality are increased in the elderly. Our preliminary results show that CSA and analgesia is a feasible option as an additional way to reduce morbidity and mortality in frail octogenarians who require RC.

Keywords

80 and over aged anesthesia bladder cancer pain postoperative procedure radical cystectomy spinal

Introduction

Bladder cancer (BC) is nowadays the fifth most common tumor in both sexes (4th in men, 10th in women), with an estimated 79,030 new cases in 2017, and the tenth leading cause of cancer death in the United States.¹ BC can occur at any age, but it is mainly a disease of aging.² Indeed it has an increasing incidence and prevalence around the sixth decade and the peak in the seventh to the eighth decade of life.² The risk of developing muscle-invasive BC (MIBC) is also age dependent. Moreover, MIBC is a lethal disease, with mortality in 85% of cases at 2 years if left untreated.³ Comorbidity, functional decline, and frailty are present in most older patients and can create an excessive risk for radical cystectomy (RC), which is considered the standard treatment of nonmetastatic MIBC.⁴ RC is associated with prolonged postoperative recovery, significant morbidity, and mortality, especially in old and very old patients.⁵ All those conditions can lead to the administration of less aggressive and effective therapies in octogenarians, such as avoidance or delay of RC and bladder-sparing treatments.⁶ Several authors have recently described that RC can be safely performed in selected elderly patients, providing similar disease control and survival outcomes comparable with those in younger patients.^7–9 Moreover, RC has demonstrated improved survival compared with nonstandard treatment in elderly patients.¹⁰ In order to improve postoperative outcomes in high-risk patients undergoing major abdominal surgery, continuous spinal anesthesia (CSA) is gaining popularity as a better tolerated technique, with a more predictable effect and lesser hemodynamic and respiratory repercussions than general anesthesia (GA) in high-risk patients.^11,12 The aim of this pilot study was to assess the feasibility, morbidity, and mortality of RC performed in CSA in the first five octogenarian patients, who were unfit for GA.

Material and methods

This is a retrospective analysis of the first five consecutive patients aged ⩾80 years, with a diagnosis of MIBC who underwent RC and ureterocutaneostomy in our hospital between 2016 and 2017. Medical examination and screening of cardiac, renal and respiratory status were performed in all cases. Frailty was assessed using the multidimensional frailty definition (score ⩾4 is indicative of frailty).^13,14 Computerized tomography of the chest, abdomen and pelvis was performed preoperatively in all patients. None of the patients underwent neoadjuvant chemotherapy in accordance with our medical oncologist. The preanesthetic risk was scored according to the American Society of Anesthesiologists physical status classification score.¹⁵ Anticoagulation and antiplatelet agents were stopped in preparation for surgery according to neurological or cardiological consultations. Surgery was performed in one metastatic patient (#3) because of recurrent and severe hematuria requiring several blood transfusions. Complications were classified according to Clavien and Dindo criteria as early (within 30 postoperative days) and late (up to 3 months of follow up).¹⁶ Perioperative mortality was considered as any death within 90 days after cystectomy. All participants were high-risk patients for GA, frail and underwent CSA and postoperative continuous analgesia (PCA). CSA is the technique of producing and maintaining neuraxial anesthesia with small doses of local anesthetics, intermittently injected into the subarachnoid space via an indwelling catheter. PCA is realized through continuous drug administration by a pump connected to the catheter. All patients signed a written informed consent.

Anesthesiological technique

Preloading was achieved by administering 500 ml of crystalloids. After sterile thoracic-lumbar field preparation with the patient in a sitting up position, the T10–T11 intervertebral space was identified using a full aseptic technique. A Spinolong polymedic kit (Temena, Varese, Italy) was used for CSA. The kit included a 21G Tuohy-shaped spinal needle and 24G intrathecal catheter. After free-flow of cerebrospinal fluid (CSF) was obtained, the catheter was inserted 3–4 cm beyond the tip of the needle. A dose of 2.5 mg hyperbaric bupivacaine plus 25 µg fentanyl was injected followed by another 2.5 mg bupivacaine 3 min later. The level of the sensory blockade was tested using pinprick tests, and if needed, further incremental doses 0.2–0.5 ml were given until an adequate level of anesthesia was obtained. Sedation was achieved with intravenous midazolam bolus 1–3 mg plus a continuous infusion of propofol (1–4 mg/kg/h). Surgery began after achieving at least Bromage scale 2.¹⁷ The sensory and motor blocks were achieved between T6 and L2, and they were tested with pinprick tests. All patients were on spontaneous breathing in Venturi masks on 40% FiO2. Hypotension was managed with noradrenaline infusion in a dose of 0.1–0.5 µg/kg/min, adjusted to maintain a mean arterial blood pressure above 70 mmHg. Analgesic intrathecal infusion started 30 min before the end of surgery with 60 mg of levo-bupivacaine (0.166%) plus fentanyl 75 µg (concentration 2 µg/ml) in 0.9% saline at a total of 36 ml. The infusion rate was of 0.2–0.5 ml/h and lasted 72 h. A tutoring video of the technique is available in the supplemental material. Postoperative pain was evaluated assessed 6, 12, and every 24 h for 3 days postoperatively, using a visual analogical scale, graduate from 0 (no pain) up to 10 (unbearable pain). Any request for painkillers was annotated.

Surgical procedure

Intravenous hydration was performed 12 h before surgery. Antibiotics prophylaxis was performed 30 min prior to incision with intravenous 1 g ceftriaxone. Low molecular weight heparin was administrated as prophylaxis against deep vein thrombosis in all cases. Open transperitoneal RC was performed according to the Skinner technique.¹⁸ Pelvic lymphadenectomy was performed in four patients. Urinary diversion was ureterocutaneostomy in all patients. Left nephroureterectomy was performed in patient #2 for concomitant upper tract carcinoma. Right colectomy was performed in patient #1 for concomitant adenocarcinoma.

Results

Demographics and characteristics of patients are summarized in Table 1. All patients were frail (mean frailty score 5.2). Mean operative time was 243 min. Only one intraoperative complication occurred, a small bowel perforation in patient #2, which was intraoperatively repaired. No patients were switched to GA, nor transferred to intensive care unit after completion of surgery or during recovery. The postoperative course is reported in Table 2. The mean blood transfusion was 3 units. Liquid oral intake was allowed 12 hours after surgery. No patients needed parenteral nutrition. No patients required opiate analgesics. Only patient #4 required a single dose of paracetamol (1 g) in postoperative day 2 for discomfort in the surgical wound. Mild respiratory acidosis was present in patients #3 and #4 in postoperative day 1, but it was not clinically significant. Patient #4 complained of self-limiting facial itching. The intrathecal catheter was removed after 72 hours in all cases. No spinal hematoma and cauda equina syndrome occurred. Meantime to first flatus was 31.4 hours, and oral feeding resumed in all patients within 3 days. No episodes of postoperative delirium were recorded. All patients were discharged home within 12 days. Early and late complications are reported in Table 3. All patients were alive 90 days after surgery.

Table 1.

Patients’ preoperative and intraoperative characteristics.

Patients	Sex	Age (years)	BMI	Comorbidity	Frailty*	ASA score	Surgical time (hours:minutes)	Transfusion rate (blood units)	Intraoperative complication	Final pathology
#1	M	86	29.6	DM; CIHD; H	5	3	4:15	2	none	Bladder: TCC pT3bN0. Colon: ADK pT2N0
#2	M	85	27.8	CIHD; CD; DM	5	3	4:25	3	small bowel perforation	Bladder: TCC pT2N0. Renal pelvis: TCC pT2
#3	F	87	19.9	SA; AF; CKF; COPD; LM	7	4	3:35	5	none	TCC pT4Nx
#4	F	80	20.1	CKF; AF; COPD	5	3	3:25	2	none	TCC pT4N2
#5	M	81	27	H; COPD	4	3	3:45	3	none	TCC pT3aN0

According to Robinson [13–14] (0 minimum; 7 maximum).

ADK, adenocarcinoma; AF, atrial fibrillation; ASA, American Society of Anesthesiologists physical status classification; BMI, body mass index; CD, cerebrovascular disease; CIHD, chronic ischemic heart disease; CKF, chronic kidney failure; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; F, female; H, hypertension; LM, multiple lung metastases; M, male; SA, severe anemia (Hb < 8 g/dl); TCC, transitional cell carcinoma.

Table 2.

Postoperative course.

Patient	Sex	Age (years)	Time to first flatus (hours)	Oral feeding (hours)	Pain at 6 hours (VAS)	Pain at 12 hours (VAS)	Pain at 24 hours (VAS)	Pain at 48 hours (VAS)	Pain at 72 hours (VAS)	Pain killers during first 72 hours	Discharging home (day)
#1	M	86	45	47	0	0	1	1	0	none	12
#2	M	85	38	45	1	0	0	1	0	none	11
#3	F	87	26	36	0	0	1	0	0	none	8
#4	F	80	22	30	0	1	0	0	3	1^*	7
#5	M	81	26	31	0	0	1	0	1	none	10

1 g paracetamol.

F, female; M, male; VAS, visual analogical scale.

Table 3.

Early (30 days) and late (90 days) complications.

Patient	Sex	Age (years)	Clavien-Dindo 1	Clavien-Dindo 2	Clavien-Dindo 3b	90 days complications
#1	M	86		BT; HF
#2	M	85		BT; HF	SMP	CKD-R
#3	F	87	RA	BT		PH
#4	F	80	WD; RA	BT
#5	M	81	WD	BT		WDR

BT, blood transfusion; CKD-R, chronic kidney disease requiring recovery in nephrology unit; F, female; HF, fever >38° C requiring long-term antibiotics; M, male; PH, persistent hematuria requiring several change of ureteral catheter; RA, respiratory acidosis requiring chest X-rays; SMP, small bowel perforation; WD, wound infections/dehiscence opened at the bedside requiring follow up; WDR, wound dehiscence repaired.

Discussion

To the best of our knowledge, this is the first report on CSA and PCA for RC in octogenarians. Management of MIBC in older patients is becoming an important issue in urooncology due to the continuous aging of the population. In fact, people aged ⩾80 years represent today 5% (62.9 million) of the more developed countries’ population, and this number is expected to double by the year 2045.¹⁹ Fonteyne and colleagues have recently demonstrated in their literature review that age should not preclude this option, but careful management is mandatory because perioperative morbidity and mortality are increased in older patients compared with younger patients.²⁰ High volume centers certainly have better outcomes, but CSA has also demonstrated excellent perioperative outcomes in high-risk patients undergoing cardiac, vascular, orthopedic, pelvic, and abdominal surgery.^11,21–23 Open abdominal surgeries are usually done under GA, but many elderly patients presented to this type of surgery have several major medical problems. Among the drawbacks of GA are the negative side effects of the drugs, and longer recovery times, all contraindications for elderly patients.²⁴ Furthermore, older patients are more sensitive to anesthetic agents and have a loss of functional reserve in all organ systems. CSA prevents needing intra and postoperative ventilation, which increase the likelihood of postoperative morbidity; in fact, respiratory morbidity is the main postoperative complication in the elderly.²⁵ Respiratory acidosis was present in two patients in our series. It is a common condition in patients undergoing major surgery under high neuraxial anesthesia and has to be considered as a Clavien grade I complication, whether it is mild, temporary, not influencing the waking state of the patients and without the need for pharmacological treatment. Furthermore, it is not correlated with a high block, because only the accessory muscles are blocked. In fact, the function of the diaphragm is not inhibited since the relative innervation depends on C3–C5, which is far from being blocked. Respiratory acidosis has been considered as a consequence of possible cephalad migration of opioid or intravenous absorption of low but continuous intrathecal fentanyl, even though it may be present in completely opioid-free thoracic spinal anesthesia.^11,26 Randomized clinical trials comparing GA versus neuraxial blockade have demonstrated that the latter reduced overall mortality by a third and also postoperative major complications (deep vein thrombosis, respiratory depression, pneumonia, pulmonary embolism, transfusion requirements, renal failure, and myocardial infarction).²⁴ De Nunzio and colleagues have demonstrated the feasibility of extraperitoneal RC in spinal anesthesia in octogenarian patients, but this was a single-shot spinal anesthesia with no postoperative analgesia.²⁷ They reported an overall morbidity rate of 13%. Our morbidity was comparable, with only seven Clavien grade 2 complications, and only one grade 3b. Friedrich-Freksa and colleagues achieved even better results (only Clavien grade 1 complications), but in a younger population.²⁸ Karl and colleagues demonstrated the feasibility of RC in exclusive spinal and epidural anesthesia in patients unfit for GA.²⁹ The advantage of postoperative CSA was clear in time to first food intake (median 3.5 days), which was comparable with ours (median 37.8 h). Thoracic CSA ensures a transperitoneal approach, and PCA provides many benefits for elderly patients, such as high analgesic efficiency, minimal effect on mental status and improved hemodynamic stability.³⁰ Thoracic CSA may have, of course, minor (possible technical difficulties with microcatheter and postdural puncture headache), and serious complications (infection, sedation, neurologic sequelae, spinal hematoma and cauda equine syndrome), but they are extremely rare.²⁴ The safety of thoracic puncture was demonstrated by Imbelloni and colleagues^31–33 They showed in a study with magnetic resonance of human spines that the place where the bone marrow practically abuts the posterior part of the subarachnoid canal is exactly between the T10–T12 level.³¹ They demonstrated a low incidence of transient paresthesia and no neurologic defect after lower thoracic spinal anesthesia regardless of the needle used (cut needle versus pencil point needle).^32,33 The use of a small intrathecal catheter, such as ours, minimizes serious complications. In fact, these complications were not present in our series. Our pilot study demonstrates that CSA is a feasible option in high-risk octogenarians who require RC; in fact, no patients have been switched to GA, surgery was completed in all cases, and all patients were managed in the ward, without needing intensive care unit admission. The PCA trough intrathecal catheter has the main advantage of not needing narcotics use, fast recovery of bowel function, and rapid oral feeding, which are typical advantages of the enhanced recovery after surgery (ERAS) protocol.³⁴ The ERAS protocol has shown to reduce the length of stay, and perioperative complications compared with the standard of care, and has a positive impact on outcomes specifically for older and frail patients.^34,35 In our series, the median length of stay was 9.6 days, and complications were mostly of low grade, with only one readmission in 90 days, due to the worsening of kidney function (patient #2, who underwent concomitant nephroureterectomy). Combing the ERAS protocol and CSA should be explored in the future to reduce the risk of postoperative complications and adverse postoperative outcomes in frail octogenarians undergoing RC.

Conclusion

This pilot study proposes CSA as a well-tolerated and effective approach in older, high risk, and frail patients undergoing RC. Further studies with a larger population are needed to confirm its beneficial role in BC patients treated with RC.

Footnotes

Acknowledgements

We thank all staff nurses in the operating room and urology department at the IRCCS INRCA, Ancona, Italy, because without their outstanding work and cooperation this study would not have been possible.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest statement

The authors declare that there is no conflict of interest.

Supplemental Material

Supplemental material for this article is available online.

ORCID iD

Daniele Castellani

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Supplementary Material

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Radical cystectomy in frail octogenarians in thoracic continuous spinal anesthesia and analgesia: a pilot study

Abstract

Background:

Methods:

Results:

Conclusions:

Keywords

Introduction

Material and methods

Anesthesiological technique

Surgical procedure

Results

Discussion

Conclusion

Footnotes

Acknowledgements

Funding

Conflict of interest statement

Supplemental Material

ORCID iD

References

Supplementary Material